Search results for: interferon alpha and beta receptor subunit 2

Authors: Stella Nkechi Ezeaku, Ifunanya Nkechi Ohamobi

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This study investigated the impact of economic crisis on education in Anambra state. The population of the study comprised of all principals and teachers in Anambra state numbering 5,887 (253 principles and 5,634 teachers). To guide the study, three research questions and one hypothesis were formulated correlational design was adopted. Stratified random sampling technique was used to select 200 principals and 300 teachers as respondents for the study. A researcher-developed instrument tagged Impact of Economic Crisis on Education questionnaire (IECEQ) was used to collect data needed for the study. The instrument was validated by experts in measurement and evaluation. The reliability of the instrument was established using randomly selected members of the population who did not take part in the study. The data obtained was analyzed using Cronbach alpha technique and reliability co-efficient of .801 and .803 was obtained. The data were analyzed using simple and Multiple Regression Analysis. The formulated hypothesis was tested at .05 level of significance. Findings revealed that: there is a significant relationship between economic crisis and realization of goals of secondary education. The result also shows that economic crisis affect students' academic performance, teachers' morale and productivity and principals' administrative capability. This study therefore concludes that certain strategies must be devised to minimize the impact of economic crisis on secondary education. It is recommended that all stakeholders to education should be more resourceful and self-sufficient in order to cushion the effects of economic crisis currently gripping most world economies Nigeria inclusive.

Keywords: impact, economic, crisis, education

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Authors: Sahar Iqrar, Malik Adeel Anwar, Zain Akram, Maria Noor

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Introduction: Oral lichen planus is a chronic inflammatory condition of unknown etiology. Oral lichen planus may be related with several other diseases. Grinspan's Syndrome is characterized by a triad of oral lichen planus, hypertension, and diabetes mellitus. Other associations reported in the literature are with chronic liver disease and, with dyslipidemia. The nature of these associations is still not fully understood. Material and methods: Study was conducted in Department of Oral Medicine, Fatima Memorial Hospital College of Medicine and Dentistry, Lahore, Pakistan. A total of n=89 clinically diagnosed patients of oral lichen planus of both gender and all age groups were recruited and detailed history were recorded in the designed performs. Results: A total of n=89 patients were taken with male to female ratio of 3:8 in which 24 were male and 65 females. Mean age was 48.8 ± 13.8 years. Age range of 10-74 years was seen. Among these patients suffering from oral lichen planus, 41.6% (n=37) had a positive history for hypertension with 59.5% (n=22) of these patients were taking different medication for their condition. Whereas Diabetes Mellitus was found in 24.7% (n=22) patients with 72.7% (n=16) of these patients using the hypoglycemic drug (oral or injectable) to control their blood glucose levels. Out of these n=89 lichen planus patients 21.3% had both hypertension and diabetes mellitus (fulfilling the criteria for Grinspan's Syndrome). Out of this Grinspan's Syndrome pool 94.7% (n=19) were taking drug atleast for one of the two conditions. Conclusion: As noticed form the medical history of the patients, most of them were using hypoglycemic drugs for diabetes mellitus and beta blockers, diuretics and calcium channel blockers for hypertension. These drugs are known for lichenoid reaction. Therefore, it should be ruled out at histopathological/ immunological and molecular level whether these patients are suffering from lichen planus or lichenoid drug reaction to truly declare them as patients with Grinspan’s Syndrome.

Keywords: diabetes mellitus, grinspan's syndrome, lichenoid drug reaction, oral lichen planus

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Authors: Shiliang Wu, Huanxin Zhang, Aditya Kumar

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There have been increasing concerns on atmospheric mercury as a toxic and bioaccumulative pollutant in the global environment. Global change, including changes in climate change, land use, land cover and wildfires activities can all have significant impacts on atmospheric mercury. In this study, we use a global chemical transport model (GEOS-Chem) to examine the potential impacts from global change on atmospheric mercury. All of these factors in the context of global change are found to have significant impacts on the long-term evolution of atmospheric mercury and can substantially alter the global source-receptor relationships for mercury. We also estimate the global Hg emissions from wildfires for present-day and the potential impacts from the 2000-2050 changes in climate, land use and land cover and Hg anthropogenic emissions by combining statistical analysis with global data on vegetation type and coverage as well as fire activities. Present global Hg wildfire emissions are estimated to be 612 Mg year-1. Africa is the dominant source region (43.8% of global emissions), followed by Eurasia (31%) and South America (16.6%). We find significant perturbations to wildfire emissions of Hg in the context of global change, driven by the projected changes in climate, land use and land cover and Hg anthropogenic emissions. 2000-2050 climate change could increase Hg emissions by 14% globally. Projected changes in land use by 2050 could decrease the global Hg emissions from wildfires by 13% mainly driven by a decline in African emissions due to significant agricultural land expansion. Future land cover changes could lead to significant increases in Hg emissions over some regions (+32% North America, +14% Africa, +13% Eurasia). Potential enrichment of terrestrial ecosystems in 2050 in response to changes in Hg anthropogenic emissions could increase Hg wildfire emissions both globally (+28%) and regionally. Our results indicate that the future evolution of climate, land use and land cover and Hg anthropogenic emissions are all important factors affecting Hg wildfire emissions in the coming decades.

Keywords: climate change, land use, land cover, wildfires

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Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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Authors: G. Shiha, S. Seif, W. Samir, K. Zalata

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Prospective Validation of the FibroTest Score in assessing Liver Fibrosis in Hepatitis C Infection with Genotype 4 FibroTest (FT) is non-invasive score of liver fibrosis that combines the quantitative results of 5 serum biochemical markers (alpha-2-macroglobulin, haptoglobin, apolipoprotein A1, gamma glutamyl transpeptidase (GGT) and bilirubin) and adjusted with the patient's age and sex in a patented algorithm to generate a measure of fibrosis. FT has been validated in patients with chronic hepatitis C (CHC) (Halfon et al., Gastroenterol. Clin Biol.( 2008), 32 6suppl 1, 22-39). The validation of fibro test ( FT) in genotype IV is not well studied. Our aim was to evaluate the performance of FibroTest in an independent prospective cohort of hepatitis C patients with genotype 4. Subject was 122 patients with CHC. All liver biopsies were scored using METAVIR system. Our fibrosis score(FT) were measured, and the performance of the cut-off score were done using ROC curve. Among patients with advanced fibrosis, the FT was identically matched with the liver biopsy in 18.6%, overestimated the stage of fibrosis in 44.2% and underestimated the stage of fibrosis in 37.7% of cases. Also in patients with no/mild fibrosis, identical matching was detected in 39.2% of cases with overestimation in 48.1% and underestimation in 12.7%. So, the overall results of the test were identical matching, overestimation and underestimation in 32%, 46.7% and 21.3% respectively. Using ROC curve it was found that (FT) at the cut-off point of 0.555 could discriminate early from advanced stages of fibrosis with an area under ROC curve (AUC) of 0.72, sensitivity of 65%, specificity of 69%, PPV of 68%, NPV of 66% and accuracy of 67%. As FibroTest Score overestimates the stage of advanced fibrosis, it should not be considered as a reliable surrogate for liver biopsy in hepatitis C infection with genotype 4.

Keywords: fibrotest, chronic Hepatitis C, genotype 4, liver biopsy

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Authors: Mohammadreza Mojtahedi

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Urban agriculture, in the face of burgeoning urban populations and unchecked urbanization, presents a promising avenue for sustainable economic, social, and environmental growth. This study, set against the backdrop of Neishabour, Iran, delves into the potential and challenges inherent in this domain. Utilizing a descriptive-analytical approach, field survey data were predominantly collated via questionnaires. The research rigor was upheld with the Delphi method affirming the validity and a Cronbach's alpha score exceeding 0.70, underscoring reliability. The study encompassed Neishabour's 2016 populace, pegged at 264,375, drawing a sample size of 384 via Cochran's formula. The findings spotlight Neishabour's pronounced agricultural prowess, as evidenced by a significance level under 0.05 and an average difference of 0.54. Engaging in urban agricultural ventures can notably elevate job quality, spur savings, bolster profitability, promote organic cultivation, and streamline production expenses. However, challenges, such as heightened land valuations for alternative uses, conflicting land engagements, security dilemmas, technical impediments, waning citizen interest, regulatory conundrums, and perceived upfront investment risks, were identified. A silver lining emerged with urban locales, especially streets and boulevards, securing average ratings of 3.90, marking them as prime contenders for urban agricultural endeavors.

Keywords: urban agriculture, sustainable development, mid-sized cities, neishabour.

Procedia PDF Downloads 57

Authors: Wania Mohammad Akram, Swetha Kannan, Urooj Shahid, Aisha Sajjad

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Ovarian ectopic pregnancy, a rare manifestation of ectopic gestation, involves the implantation of a fertilized egg on the ovarian surface. This condition poses diagnostic challenges and is associated with significant maternal morbidity if not promptly managed. This report presents the case of a 33-year-old nulliparous woman with a history of polycystic ovary syndrome (PCOS) undergoing ovulation induction therapy. Following her first conception in October 2021, she presented with symptoms of per vaginal spotting and low back pain, prompting a diagnosis of left adnexal ectopic pregnancy confirmed by transvaginal ultrasound and serum beta-human chorionic gonadotropin (B-HCG) levels. Medical management with methotrexate was initiated successfully. In August 2022, the patient conceived again, with subsequent ultrasound revealing a large pelvic collection suggestive of a complex ectopic pregnancy involving both ovaries. Despite initial stability, she developed abdominal pain necessitating emergency laparoscopy, which revealed an ovarian ectopic pregnancy with hemoperitoneum. Laparotomy was performed due to the complexity of the presentation, and histopathology confirmed viable chorionic villi within ovarian tissue. This case underscores the clinical management challenges posed by ovarian ectopic pregnancies, particularly in patients with previous ectopic pregnancies. The discussion reviews current literature on diagnostic modalities, treatment strategies, and outcomes associated with ovarian ectopic pregnancies, emphasizing the role of surgical intervention in cases refractory to conservative management. Tailored approaches considering individual patient factors are crucial to optimize outcomes and preserve fertility in such complex scenarios.

Keywords: obgyn, ovarian ectopic pregnancy, laproscopy, pcos

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Authors: Wessam H. Abd-Elsalam, Mona M. Saber, Samar M. Abouelatta

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Non-steroidal anti-inflammatory drugs (NSAIDs) are considered a double edged sword in inflammatory bowel diseases (IBDs). Some studies reported their advantageous effect in decreasing inflammation, and other studies reported that their use is associated with colitis aggravation. This study aimed to use specifically formulated trehalose-based nano-carriers that targets the colon in an attempt to alleviate inflammation caused by NSAIDs. L-α-phosphatidylcholine (PL), trehalose, and transcutol were used to prepare the trehalosomes (THs), which were also loaded with Tenoxicam(TXM) as a model NSAID. To optimize the formulation variables, a full 23 factorial design, using Design-Expert® software, was performed. The optimized formulation composed of trehalose: PL at a weight ratio of 1:1, 377.72 mg transcutol, and sonicated for 4 min, possessed a spherical shape with a size of 268.61 nm and EE% of 97.83% and released 70.22% of its drug content over 24 h. The superior protective action of TXM loaded THs compared to TXM suspension and drug-free THs was shown by the inhibition of the inflammatory biomarkers, namely; IL-1ß, IL-6, and TNF-alpha levels, as well as oxidative stress markers, measured as GSH and MDA. Improved histopathology of the colonic tissue in male New Zealand rabbits also confirmed the superiority of the TXM loaded THs compared to the unformulated drug or the drug free nano-carriers. Our findings highlight the prosperous role of THs in colon targeting and its anti-inflammatory characteristics in guarding against possible NSAIDs-driven exacerbation of colitis.

Keywords: inflammatory bowel disease, trehalose, trehalosomes, colon targeting

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Authors: Mohamed Moussaoui

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A series of thirty-one potential inhibitors targeting the epidermal growth factor receptor kinase (EGFR), derived from quinazoline, underwent 3D-QSAR analysis using CoMFA and CoMSIA methodologies. The training and test sets of quinazoline derivatives were utilized to construct and validate the QSAR models, respectively, with dataset alignment performed using the lowest energy conformer of the most active compound. The best-performing CoMFA and CoMSIA models demonstrated impressive determination coefficients, with R² values of 0.981 and 0.978, respectively, and Leave One Out cross-validation determination coefficients, Q², of 0.645 and 0.729, respectively. Furthermore, external validation using a test set of five compounds yielded predicted determination coefficients, R² test, of 0.929 and 0.909 for CoMFA and CoMSIA, respectively. Building upon these promising results, eighteen new compounds were designed and assessed for drug likeness and ADMET properties through in silico methods. Additionally, molecular docking studies were conducted to elucidate the binding interactions between the selected compounds and the enzyme. Detailed molecular dynamics simulations were performed to analyze the stability, conformational changes, and binding interactions of the quinazoline derivatives with the EGFR kinase. These simulations provided deeper insights into the dynamic behavior of the compounds within the active site. This comprehensive analysis enhances the understanding of quinazoline derivatives as potential anti-cancer agents and provides valuable insights for lead optimization in the early stages of drug discovery, particularly for developing highly potent anticancer therapeutics

Keywords: 3D-QSAR, CoMFA, CoMSIA, ADMET, molecular docking, quinazoline, molecular dynamic, egfr inhibitors, lung cancer, anticancer

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Authors: Mahnaz Zarein, Hamed Shoorei

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Background: Malathion is one of the most toxic agents widely used in agriculture throughout the world. This agent has adverse effects on the functions of multiple organs such as the reproductive system in both male and female genders. On the one hand, daily use of antioxidant supplementations such as hesperidin is capable to neutralize the deleterious impacts of malathion. Therefore, in this experimental study, the protective effects of hesperidin against ovarian toxicity induced by malathion were investigated. Material & Methods: Balb/c adult mice (n=32) were randomly divided into 4 groups including 1) the control group, treated with normal saline, 2) the Mal group, treated with 30mg/kg malathion, daily for 1 month, 3) Mal + Hes group, treated with 20 mg/kg malathion and 20 mg/kg hesperidin, daily for 1 month, and 5) Hes group, treated with 20 mg/kg hesperidin. At the end of the experimental period, mice were anesthetized and their drops of blood were collected to the assessment of some hormones such as LH, FSH, E2, and P4. Also, the right ovaries were used to H&E staining, and the left ovaries were used for IHC staining (PCNA and FSHR). Results: Histopathological assessments showed that the number of follicles, i.e. primordial, primary, and secondary, significantly decreased, while the atretic follicle counts remarkably increased compared to the control group (p<0.05). Hormonal levels revealed that the production of all mentioned hormones decreased in the Mal group in comparison with the control group (p<0.05). The expression of PCNA, as a proliferative marker, and FHSR, as a marker showing maturation, decreased when mice received malathion compared to the control group (p<0.05). Interestingly, treatment with hesperidin significantly neutralized the adverse effects of malathion on all mentioned parameters. Conclusion: Daily use of antioxidant supplementations such as hesperidin could alleviate the ovarian toxicity induced by malathion.

Keywords: malathion, ovary, antioxidant hesperidin, FSHR PCNA, ovary

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Authors: Rohit Singh Dangi, Ravi Kant Pal, Monica Sundd

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Acyl-CoA binding protein (ACBP) is a housekeeping protein which functions as an intracellular carrier of acyl-CoA esters. Given the fact that the amastigote stage (blood stage) of Leishmania depends largely on fatty acids as the energy source, of which a large part is derived from its host, these proteins might have an important role in its survival. In Leishmania major, genome sequencing suggests the presence of six ACBPs, whose function remains largely unknown. For functional and structural characterization, one of the ACBP genes was cloned, and the protein was expressed and purified heterologously. Acyl-CoA ester binding and stoichiometry were analyzed by isothermal titration calorimetry and Dynamic light scattering. Our results shed light on high affinity of ACBP towards longer acyl-CoA esters, such as myristoyl-CoA to arachidonoyl-CoA with single binding site. To understand the binding mechanism & dynamics, Nuclear magnetic resonance assignments of this protein are being done. The protein's crystal structure was determined at 1.5Å resolution and revealed a classical topology for ACBP, containing four alpha-helical bundles. In the binding pocket, the loop between the first and the second helix (16 – 26AA) is four residues longer from other extensively studied ACBPs (PfACBP) and it curls upwards towards the pantothenate moiety of CoA to provide a large tunnel space for long acyl chain insertion.

Keywords: acyl-coa binding protein (ACBP), acyl-coa esters, crystal structure, isothermal titration, calorimetry, Leishmania

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Authors: Sedigheh Salemi, Mahnaz Sanjari, Maryam Aalaa, Mohammad Mirzabeigi

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Clinical governance is the framework within which the health service provider is required to ongoing accountability and improvement of the quality of their services. This cross-sectional study was conducted in 661 nurses who work in government hospitals from 35 hospitals of 9 provinces in Iran. The study was approved by the Nursing Council and was carried out with the authorization of the Research Ethics Committee. The questionnaire included 24 questions in which 4 questions focused on clinical governance defining from the nurses' perspective. The reliability was evaluated by Cronbach's alpha (α=0/83). Statistical analyzes were performed, using SPSS version 16. Approximately 40% of nurses correctly answered that clinical governance is not "system of punishment and rewards for the staff". The most nurses believed that "clinical efficacy" is one of the main components of clinical governance. A few of nurses correctly responded that "Evidence Based Practice" and "management" is not part of clinical governance. The small number of nurses correctly answered that the "maintenance of patient records" and "to recognize the adverse effects" is not the role of nurse in clinical governance. Most "do not know" answer was to the "maintenance of patient records". The most nurses unanimously believed that the implementation of clinical governance led to "promoting the quality of care". About a third of nurses correctly stated that the implementation of clinical governance will not lead to "an increase in salaries and benefits of the medical team". As a member of the health team, nurses are responsible in terms of participation in quality improvement and it is necessary to create an environment in which clinical care will flourish and serve to preserve the high standards.

Keywords: clinical governance, nurses, salary, health team

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Authors: B. O. Diyaolu

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Viability and competency during competition is the dream of every team sports so as to have a good result. But it seems factors abound which deter the performance of even a good sports team. Different individuals with different state of mind all come together to perform in team sports with different degree of satisfaction. This study investigated the role of satisfaction on performance among Afe Babalola University team sports. Descriptive survey research design was used and the population consists of all male and female athletes in the team sports that participated in the last 2019 Ekiti State Higher Institution games (ESHIGA). Total enumeration technique was used for the three team sports; football (44), basketball (24) and volleyball (24). A total of 92 participants were involved in the research. The instrument used for the study was a modified Athlete Satisfaction Scale (ASS). The questionnaire was divided into two sections. The Cronbach’s Alpha reliability coefficient of 0.71 was obtained. The hypotheses were tested at 0.05 significant levels. The completed questionnaire was collated, coded, and analyzed using descriptive statistics of frequency counts and percentage and inferential statistics of chi-square (X²). Findings of this study revealed that satisfaction significantly influences team sports performance among Athletes of Afe Babalola University. The responsibility of satisfying athlete lies on the coaches, fans, sports administrators as well as organizers of such event, as it is not only financial reward that gives satisfaction. The performance of a team sports is quiet important and its being determined by the degree of satisfaction of each individual that make up the team. All effort must be made to satisfy athlete in order to guarantee optimum performance.

Keywords: athlete satisfaction, optimum achievement, optimum performance, sports performance and team sports

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Authors: Rekaya A. Shabbir, Marco Mingarelli, Glenn Flux, Ananya Choudhury, Tim A. D. Smith

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Introduction: Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials.

Keywords: cancer cells, dose distributions, radionuclide therapy, targeted gold nanoparticles

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Authors: Ayşe Defne Öz, Özlem Bozkurt

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Alzheimer's Disease (AD) is counted as one of the most important global health problems and the main cause of dementia. The term dementia refers to a wide spectrum of disorders characterized by global, chronic, and generally irreversible cognitive deterioration. It is estimated that %60 % to 80 of the cases of dementia are because of AD. Alzheimer's is a slowly progressive brain disease. The reason for AD is unknown to the author's best knowledge, yet it is one of the topics that is most researched. AD shows the histopathologically abnormal accumulation of the protein beta-amyloid (plague) outside neurons and twisted strands of the protein tau (tangles) inside neurons in the brain. These changes are accompanied by damage to the brain tissue and the death of neurons. AD causes people to have difficulty remembering names or conversations. Some of the later symptoms are difficulty in talking and walking. Alzheimer's Disease is elevated by the illness and mortality of COVID-19. COVID-19 has affected many lives globally and had profound effects on human lives. COVID-19 is caused by SARS-CoV-2, which is a virus that attacks the respiratory and central nervous system and has neuroinvasive potential. More than %80 of COVID-19 patients have ageusia or anosmia, representing the pathognomic features of the disease. Patients with dementia are frail, and with the COVID-19 pandemic, including isolation, cognitive decline may exacerbate. Furthermore, patients with AD can be unable to follow the directions, such as covering their mouth and nose while coughing and can live in nursing homes which makes them more open to being infected. As COVID-19 is highly infectious and its management requires isolation and quarantine, the need for caregivers for AD management conflicts with that of COVID-19 and adds an extra burden on AD patients, caregivers, families, society, and the economy. Due to the entry of SARS-CoV-2 into the central nervous system, inflammation caused by COVID-19, prolonged hospitalization, and delirium, it has been reported that COVID-19 causes many neurological disorders and predisposition to AD.

Keywords: Alzheimer's disease, COVID-19, dementia, SARS-CoV-2

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Authors: Abdolmajid Mosleh, Afzal Ghasimi

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The purpose of this research is to investigate and identify effective factors that can improve the quality of personal performance in industrial companies. In the present study, it was assumed that the hidden variables of talent management could be explained by an important part of the variance in improving the quality of employee performance. This research is targeted in terms of applied research. The statistical population of the research is SAIPA automobile company with a number (N=10291); the sample of 380 people was selected based on the Cochran formula in a random sampling method among employed people. The measurement tool in this research was a questionnaire of 33 items with a control questionnaire that included two talent management departments (talent identification and talent exploitation) and improvements in staff performance (enhancement of technical and specialized capabilities, managerial capability, organizational interaction, and communication). The reliability of the internal consistency method was confirmed by the Cronbach's alpha coefficient and the two half-ways. In order to determine the validity of the questionnaire structure, confirmatory factor analysis was used. Based on the results of the data analysis, the effect of talent management on improving the quality of staff performance was confirmed. Based on the results of inferential statistics and structural equations of the proposed model, it had high fitness.

Keywords: employee performance, talent management, performance improvement, SAIPA automobile manufacturing company

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Authors: Roseline Chizoba Onuoha, Rose Ngozi Uzoka

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This study aimed at investigating perceived effect of physical exercise on healthy well-being of pregnant mothers in Imo state. The study was guided by three research questions and three null hypotheses tested at 0.05 level of significance. The study was a quasi-experimental non-equivalent control group design involving pre and post tests. A sample of 92 pregnant women drawn from a total population of 922 registered pregnant women in ten randomly selected health centers in Imo State through multistage sampling technique was used. A 41 item structured instrument titled Physical Exercise Pregnancy Test (PEPT) was used for the study. The PEPT was validated by three experts from measurement and evaluation, educational psychology and health education. Crombach Alpha method was used to determine the reliability of Physical Exercise Pregnancy Test (PEPT) and reliability index of 0.82 was obtained. Mean and standard deviation were used to answer the research questions; while Analysis of Covariance (ANCOVA) was used in analyzing the hypotheses. Findings of the study revealed that physical exercise affects physical, social and emotional wellbeing scores of pregnant women. The study also indicated that intervention using physical exercise significantly enhanced healthy well-being scores of pregnant mothers who were exposed to physical exercise than those who received conventional health talks; Location has no significant interaction effect on the mean well-being scores of pregnant women via PEPT. Among recommendations made were that pregnant women should participate in physical exercise.

Keywords: educational psychology, Imo state, Physical exercise, pregnant women

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Authors: Surya R. Niraula, Devendra B Chhetry, Girish K. Singh, S. Nagesh, Frederick A. Connell

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Background: Although random sampling is generally considered to be the gold standard for population-based research, the majority of drug abuse research is based on non-random sampling despite the well-known limitations of this kind of sampling. Method: We compared the statistical properties of two surveys of drug abuse in the same community: one using snowball sampling of drug users who then identified “friend controls” and the other using a random sample of non-drug users (controls) who then identified “friend cases.” Models to predict drug abuse based on risk factors were developed for each data set using conditional logistic regression. We compared the precision of each model using bootstrapping method and the predictive properties of each model using receiver operating characteristics (ROC) curves. Results: Analysis of 100 random bootstrap samples drawn from the snowball-sample data set showed a wide variation in the standard errors of the beta coefficients of the predictive model, none of which achieved statistical significance. One the other hand, bootstrap analysis of the random-sample data set showed less variation, and did not change the significance of the predictors at the 5% level when compared to the non-bootstrap analysis. Comparison of the area under the ROC curves using the model derived from the random-sample data set was similar when fitted to either data set (0.93, for random-sample data vs. 0.91 for snowball-sample data, p=0.35); however, when the model derived from the snowball-sample data set was fitted to each of the data sets, the areas under the curve were significantly different (0.98 vs. 0.83, p < .001). Conclusion: The proposed method of random sampling of controls appears to be superior from a statistical perspective to snowball sampling and may represent a viable alternative to snowball sampling.

Keywords: drug abuse, matched case-control study, non-probability sampling, probability sampling

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Authors: Kai Pei Huang, Ting Chung Hung, Li Ching Wu

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Amyloidosis refers to a variety of conditions wherein amyloid proteins are abnormally deposited in organ or tissues and cause harm. Among the several forms of amyloidosis, the principal types of that in inpatient medical services are the AL amyloidosis (primary) and AA amyloidois (secondary). AL Amyloidois is due to deposition of protein derived from overproduction of immunoglobulin light chain in plasma cell myeloma. Furthermore, it is a systemic disorder that can present with a variety of symptoms, including heavy proteinemia and edema, heptosplenomegaly, otherwise unexplained heart failure. We reported a 78-year-old female presenting dysuria, oliguria and leg edema for several months. Laboratory data showed proteinuria (UPCR:1679.8), leukocytosis (WBC:16.2 x 10^3/uL), results of serum urea nitrogen (39mg/dL), creatinine (0.76 mg/dL), IgG (748 mg/dL.), IgA (635 mg/dL), IgM (63 mg/dL), kappa light chain(18.8 mg/dL), lambda light chain (110.0 mg/dL) and kappa/lambda ratio (0.17). Renal biopsy found amyloid fibrils in glomerular mesangial area, and Congo red stain highlights amyloid deposition in glomeruli. Additional lab studies included serum protein electrophoresis, which shows a major monoclonal peak in β region and minor small peak in gamma region, and the immunotyping studies for serum showed two IgA/λ type. We treated sample with beta-mercaptoethanol which reducing the polymerized immunoglobulin to clarify two IgA/λ are secreted from the same plasma cell clone in bone marrow. Later examination confirmed it existed plasma cell infiltration in bone marrow, and the immunohistochemical staining showed monotypic for λ light chain and are positive for IgA. All findings mentioned above reveal it is a case of plasma cell myeloma with λ Light Chain Amyloidosis.

Keywords: amyloidosis, immunoglobulin light chain, plasma cell myeloma, serum protein electrophoresis

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Authors: Monika Soni, Shovonlal Bhowmick, Chandra Bhattacharya, Jitendra Sharma, Prafulla Dutta, Jagadish Mahanta

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Aedes aegypti and Aedes albopictus are considered as two major vectors to transmit dengue virus. In North-east India, two states viz. Assam and Arunachal Pradesh are known to be high endemic zone for dengue and Chikungunya viral infection. The taxonomical classification of medically important vectors are important for mapping of actual evolutionary trends and epidemiological studies. However, misidentification of mosquito species in field-collected mosquito specimens could have a negative impact which may affect vector-borne disease control policy. DNA barcoding is a prominent method to record available species, differentiate from new addition and change of population structure. In this study, a combined approach of a morphological and molecular technique of DNA barcoding was adopted to explore sequence variation in mitochondrial cytochrome c oxidase subunit I (COI) gene within dengue vectors. The study has revealed the map distribution of the dengue vector from two states i.e. Assam and Arunachal Pradesh, India. Approximate five hundred mosquito specimens were collected from different parts of two states, and their morphological features were compared with the taxonomic keys. The analysis of detailed taxonomic study revealed identification of two species Aedes aegypti and Aedes albopictus. The species aegypti comprised of 66.6% of the specimen and represented as dominant dengue vector species. The sequences obtained through standard DNA barcoding protocol were compared with public databases, viz. GenBank and BOLD. The sequences of all Aedes albopictus have shown 100% similarity whereas sequence of Aedes aegypti has shown 99.77 - 100% similarity of COI gene with that of different geographically located same species based on BOLD database search. From dengue prevalent different geographical regions fifty-nine sequences were retrieved from NCBI and BOLD databases of the same and related taxa to determine the evolutionary distance model based on the phylogenetic analysis. Neighbor-Joining (NJ) and Maximum Likelihood (ML) phylogenetic tree was constructed in MEGA6.06 software with 1000 bootstrap replicates using Kimura-2-Parameter model. Data were analyzed for sequence divergence and found that intraspecific divergence ranged from 0.0 to 2.0% and interspecific divergence ranged from 11.0 to 12.0%. The transitional and transversional substitutions were tested individually. The sequences were deposited in NCBI: GenBank database. This observation claimed the first DNA barcoding analysis of Aedes mosquitoes from North-eastern states in India and also confirmed the range expansion of two important mosquito species. Overall, this study insight into the molecular ecology of the dengue vectors from North-eastern India which will enhance the understanding to improve the existing entomological surveillance and vector incrimination program.

Keywords: COI, dengue vectors, DNA barcoding, molecular identification, North-east India, phylogenetics

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Authors: Eduardo Kanagushiku Pereira, Frank Gregory Cavalcante da Silva, Barbara Soares Gonçalves, Ana Lúcia Bergamasco Galastri, Ronei Luciano Mamoni

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The inflammatory response initiates after the recognition of pathogens by receptors expressed by innate immune cells. Among these receptors, the NLRP3 was associated with the recognition of pathogenic fungi in experimental models. NLRP3 operates forming a multiproteic complex called inflammasome, which actives caspase-1, responsible for the production of the inflammatory cytokines IL-1beta and IL-18. In this study, we aimed to investigate the involvement of NLRP3 in the inflammatory response elicited in macrophages against Paracoccidioides brasiliensis (Pb), the etiologic agent of PCM. Macrophages were differentiated from THP-1 cells by treatment with phorbol-myristate-acetate. Following differentiation, macrophages were stimulated by Pb yeast cells for 24 hours, after previous treatment with specific NLRP3 (3,4-methylenedioxy-beta-nitrostyrene) and/or caspase-1 (VX-765) inhibitors, or specific inhibitors of pathways involved in NLRP3 activation such as: Reactive Oxigen Species (ROS) production (N-Acetyl-L-cysteine), K+ efflux (Glibenclamide) or phagossome acidification (Bafilomycin). Quantification of IL-1beta and IL-18 in supernatants was performed by ELISA. Our results showed that the production of IL-1beta and IL-18 by THP-1-derived-macrophages stimulated with Pb yeast cells was dependent on NLRP3 and caspase-1 activation, once the presence of their specific inhibitors diminished the production of these cytokines. Furthermore, we found that the major pathways involved in NLRP3 activation, after Pb recognition, were dependent on ROS production and K+ efflux. In conclusion, our results showed that NLRP3 participates in the recognition of Pb yeast cells by macrophages, leading to the activation of the NLRP3-inflammasome and production of IL-1beta and IL-18. Together, these cytokines can induce an inflammatory response against P. brasiliensis, essential for the establishment of the initial inflammatory response and for the development of the subsequent acquired immune response.

Keywords: inflammation, IL-1beta, IL-18, NLRP3, Paracoccidioidomycosis

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Authors: Pureun-Haneul Lee, Byeong-Gon Kim, Sun-Hye Lee, An-Soo Jang

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Background: Nanoparticles may pose adverse health effects due to particulate matter inhalation. Nanoparticle exposure induces cell and tissue damage, causing local and systemic inflammatory responses. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1β (IL-1β) into its mature form and may signal acute and chronic immune responses to nanoparticles. Objective: The aim of the study was to identify whether nanoparticles exaggerates inflammasome pathway leading to airway inflammation and hyperresponsiveness in an allergic mice model of asthma. Methods: Mice were treated with saline (sham), OVA-sensitized and challenged (OVA), or titanium dioxide nanoparticles. Lung interleukin 1 beta (IL-1β), interleukin 18 (IL-18), NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and caspase-1 levels were assessed with Western Blot. Caspase-1 was checked by immunohistochemical staining. Reactive oxygen species were measured for the marker 8-isoprostane and carbonyl by ELISA. Results: Airway inflammation and hyperresponsiveness increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. TiO2 nanoparticles treatment increased IL-1β and IL-18 protein expression in OVA-sensitized/challenged mice. TiO2 nanoparticles augmented the expression of NLRP3 and caspase-1 leading to the formation of an active caspase-1 in the lung. Lung caspase-1 expression was increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. Reactive oxygen species was increased in OVA-sensitized/challenged mice and in OVA-sensitized/challenged plus TiO2 exposed mice. Conclusion: Our data demonstrate that inflammasome pathway activates in asthmatic lungs following nanoparticles exposure, suggesting that targeting the inflammasome may help control nanoparticles-induced airway inflammation and responsiveness.

Keywords: bronchial asthma, inflammation, inflammasome, nanoparticles

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Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

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Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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Authors: Lida Moghaddam-Banaem, Mahmood Tavoosi, Soheila Khalili

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Objective: The main objective of this study was designing a breast cancer health literacy questionnaire and assess its psychometric properties. Methods: A comprehensive literature review was performed to develop a primary questionnaire consisting of five domains. Qualitative and quantitative content validity were assessed by relevant experts, and after some modifications, the content validity index (CVI) and content validity ratio (CVR) were calculated. Qualitative and quantitative face validity were evaluated by a number of patients, and the impact score for each item was calculated. 225 women with breast cancer were asked to fill out the questionnaire and construct validity was determined by using exploratory factor analysis. The reliability was tested by Cronbach's alpha coefficient. Results: A 36-item questionnaire with five domains of reading, having access, understanding, assessing/judgment, and decision making/behavior was designed. 2 items were omitted in the qualitative content validity process. All items achieved optimum values in CVI, CVR and impact scores. Content and face validity of the questionnaire were confirmed too. According to the exploratory factor analysis, the five-factor solution accounted for 64.98 percent of the observed variance. Conclusion: Due to the obtained satisfactory validity and reliability, this tool can be used to assess health literacy in women with breast cancer. Health policy makers can use these findings for improving health-related behaviors in breast cancer patients.

Keywords: health literacy, breast cancer, questionnaire, psychometric properties

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Authors: Emmanuel Ukpe, S. M. F. D. Syed Mustapha

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Trust in an organization has been perceived as one of the key factors behind knowledge sharing, mainly in an unstructured work environment. In an informal working environment, to instill trust among individuals is a challenge and even more in the virtual environment. The study has contributed in developing the framework for building trust in an unstructured organization in performing knowledge sharing in a virtual environment. The artifact called KAPE (Knowledge Acquisition, Processing, and Exchange) was developed for knowledge sharing for the informal organization where the framework was incorporated. It applies to Cassava farmers to facilitate knowledge sharing using web-based platform. A survey was conducted; data were collected from 382 farmers from 21 farm communities. Multiple regression technique, Cronbach’s Alpha reliability test; Tukey’s Honestly significant difference (HSD) analysis; one way Analysis of Variance (ANOVA), and all trust acceptable measures (TAM) were used to test the hypothesis and to determine noteworthy relationships. The results show a significant difference when there is a trust in knowledge sharing between farmers, the ones who have high in trust acceptable factors found in the model (M = 3.66 SD = .93) and the ones who have low on trust acceptable factors (M = 2.08 SD = .28), (t (48) = 5.69, p = .00). Furthermore, when applying Cognitive Expectancy Theory, the farmers with cognitive-consonance show higher level of trust and satisfaction with knowledge and information from KAPE, as compared with a low level of cognitive-dissonance. These results imply that the adopted trust model KAPE positively improved knowledge sharing activities in an informal environment amongst rural farmers.

Keywords: trust, knowledge, sharing, knowledge acquisition, processing and exchange, KAPE

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Authors: Jonathan Doku

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The study's goal was to evaluate construction site safety management in Ghana. The construction sector has long been seen as a high-risk business. It entails a variety of hazardous and challenging labor duties, such as lifting and working at a height, among others. The accident rate is a standard indicator for comparing the safety performance of construction projects. Because of its high-risk and fast-changing work environment, the construction business is regarded as one of the industries with the highest accident rates in the world. Many mishaps and work-related diseases have occurred there, and construction workers are particularly vulnerable to catastrophic calamities such as falls, collapses, and burial. The study's main goals were to discover characteristics that have a substantial impact on construction site safety, to evaluate the safety management methods utilized on construction sites, and to assess the obstacles associated with construction site safety management. The study was conducted using a quantitative research method and a purposive sampling strategy. Google forms were used to distribute self-administered surveys to 85 responders. 72 of the 85 questionnaires were completed and submitted for analysis, accounting for 84.7 percent of the total. The variables were analyzed using descriptive statistics, mean score ranking, and Cronbach's Alpha Coefficient to ensure the scale's reliability. The formal safety organization structure and the Safety checklist were identified as the key practices of safety management on site as part of the study goals. In addition, it was discovered that the most serious problem with safety management is ineffective supervision. To guarantee efficient monitoring and proper implementation of health and safety rules on building sites, management must be on the ball.

Keywords: construction, safety, risk, management

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Authors: Dwitya Elvira, Raveinal Masri, Rohayat Bilmahdi

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Human Immunodeficiency Virus (HIV) pandemic increased significantly worldwide. The rise in cases of HIV/AIDS was also followed by an increase in the incidence of opportunistic infection, with tuberculosis being the most opportunistic infection found in HIV/AIDS and the main cause of mortality in HIV/AIDS patients. Diagnosis of tuberculosis in HIV/AIDS patients is often difficult because of the uncommon symptom in HIV/AIDS patients compared to those without the disease. Thus, diagnostic tools are required that are more effective and efficient to diagnose tuberculosis in HIV/AIDS. CXCL-10/IP-10 is a chemokine that binds to the CXCR3 receptor found in HIV/AIDS patients with a weakened immune system. Tuberculosis infection in HIV/AIDS activates chemokine IP-10 in urine, which is used as a marker for diagnosis of infection. The aim of this study was to prove whether IP-10 urine can be a biomarker diagnosis of active lung tuberculosis in HIV-AIDS patients. Design of this study is a cross sectional study involving HIV/AIDS patients with lung tuberculosis as the subject of this study. Forty-seven HIV/AIDS patients with tuberculosis based on clinical and biochemical laboratory were asked to collect urine samples and IP-10/CXCL-10 urine being measured using ELISA method with 18 healthy human urine samples as control. Forty-seven patients diagnosed as HIV/AIDS were included as a subject of this study. HIV/AIDS were more common in male than in women with the percentage in male 85.1% vs. 14.5% of women. In this study, most diagnosed patients were aged 31-40 years old, followed by those 21-30 years, and > 40 years old, with one case diagnosed at age less than 20 years of age. From the result of the urine IP-10 using ELISA method, there was significant increase of the mean value of IP-10 urine in patients with TB-HIV/AIDS co-infection compared to the healthy control with mean 61.05 pg/mL ± 78.01 pg/mL vs. mean 17.2 pg/mL. Based on this research, there was significant increase of urine IP-10/CXCL-10 in active lung tuberculosis with HIV/AIDS compared to the healthy control. From this finding, it is necessary to conduct further research into whether urine IP-10/CXCL-10 plays a significant role in TB-HIV/AIDS co-infection, which can also be used as a biomarker in the early diagnosis of TB-HIV.

Keywords: chemokine, HIV/AIDS, IP-10 urine, tuberculosis

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Authors: Masoumeh Kazemi

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Depression is one of the most common mental disorders that damage mental health. In addition to mental distress, mental health damage affects other dimensions of human health, including physical and social health. According to the national study of diseases and injuries in Iran, the third health problem of the country is depression. The purpose of this study was to measure the level of depression in people referred to Karaj psychiatric treatment centers, and to investigate the relationship between depression and drug and alcohol consumption. The statistical population included 5000 people. Morgan table was used to determine the sample size. The research questions sought to identify the relationship between depression and factors such as drug and alcohol use, employment and marital status, and gender. Beck standard questionnaire was used to collect complete information. Cronbach's alpha coefficient was used to confirm the reliability of the questionnaire. To test research hypotheses, non-parametric methods of correlation coefficient, Spearman's rank, Mann-Whitney and Kruskal-Wallis tests were used. The results of using SPSS statistical software showed that there is a direct relationship between depression and drug and alcohol use. Also, the rate of depression was higher in women, widows and unemployed people. Finally, by conducting the present study, it is suggested that people use the following treatments in combination for effective recovery: 1. Cognitive Behavioral Therapy (CBT) 2. Interpersonal Therapy (IPT) 3. Treatment with appropriate medication 4. Special light therapy 5. Electric shock treatment (in acute and exceptional cases) 6. Self-help

Keywords: alcohol, depression, drug, Iran

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Authors: Seyede Sanaz Seyedebrahimi, Shima Rahimi, Shohreh Fakhari, Ali Jalili

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Background: CXCR4, as a chemokine receptor, plays well-known roles in various types of cancers. Several studies have been conducted to overcome CXCR4 axis acts in multiple myeloma (MM) pathogenesis and progression. Dexamethasone, a standard treatment for multiple myeloma, has been shown to increase CXCR4 levels in multiple myeloma cell lines. Herein, we focused on the effects of metformin and dexamethasone on CXCR4 at the cellular level and the migration rate of cell lines after exposure to a combination compared to single-agent models. Materials and Method: Multiple myeloma cell lines (U266 and RPMI8226) were cultured with different metformin and dexamethasone concentrations in single-agent and combination models. The simultaneous combination doses were calculated by CompuSyn software. Cell surface and mRNA expression of CXCR4 were determined using flow cytometry and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay, respectively. The Transwell cell migration assay evaluated the migration ability. Results: In concurred with previous studies, our results showed a dexamethasone up-regulation effect on CXCR4 in a dose-dependent manner. Although, the metformin single-agent model could reduce CXCR4 expression of U266 and RPMI8226 in cell surface and mRNA expression level. Moreover, the administration of metformin and dexamethasone simultaneously exerted a higher suppression effect on CXCR4 expression than the metformin single-agent model. The migration rate through the combination model's matrigel membrane was remarkably lower than the metformin and dexamethasone single-agent model. Discussion: According to our findings, the combination of metformin and dexamethasone effectively inhibited dexamethasone-induced CXCR4 expression in multiple myeloma cell lines. As a result, metformin may be counted as an alternative medicine combined with other chemotherapies to combat multiple myeloma. However, more research is required.

Keywords: CXCR4, dexamethasone, metformin, migration, multiple myeloma

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Authors: Rachmat Mauludin, Nurmazidah

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Background and purpose: Famotidine is an H2 receptor blocker. Absorption orally is rapid enough, but famotidine can be degraded by stomach acid causing dose reduction until 35.8% after 50 minutes. This drug also undergoes first-pass metabolism which reduced its bio availability only until 40-50%. To overcome these problems, Solid Lipid Nano particles (SLNs) as alternative delivery systems can be formulated. SLNs is a lipid-based drug delivery technology with 50-1000 nm particle size, where the drug incorporated into the bio compatible lipids and the lipid particles are stabilized using appropriate stabilizers. When the particle size is 200 nm or below, lipid containing famotidine can be absorbed through the lymphatic vessels to the subclavian vein, so first-pass metabolism can be avoided. Method: Famotidine SLNs with various compositions of stabilizer was prepared using a high-speed homogenization and sonication method. Then, the particle size distribution, zeta potential, entrapment efficiency, particle morphology and in vitro release profiles were evaluated. Optimization of sonication time also carried out. Result: Particle size of SLN by Particle Size Analyzer was in range 114.6 up to 455.267 nm. Ultrasonicated SLNs within 5 minutes generated smaller particle size than SLNs which was ultrasonicated for 10 and 15 minutes. Entrapment efficiency of SLNs were 74.17 up to 79.45%. Particle morphology of the SLNs was spherical and distributed individually. Release study of Famotidine revealed that in acid medium, 28.89 up to 80.55% of famotidine could be released after 2 hours. Nevertheless in basic medium, famotidine was released 40.5 up to 86.88% in the same period. Conclusion: The best formula was SLNs which stabilized by 4% Poloxamer 188 and 1 % Span 20, that had particle size 114.6 nm in diameter, 77.14% famotidine entrapped, and the particle morphology was spherical and distributed individually. SLNs with the best drug release profile was SLNs which stabilized by 4% Eudragit L 100-55 and 1% Tween 80 which had released 36.34 % in pH 1.2 solution, and 74.13% in pH 7.4 solution after 2 hours. The optimum sonication time was 5 minutes.

Keywords: famotodine, SLN, high speed homogenization, particle size, release study

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