Search results for: sickle cell disease (SCD)

Authors: Ibrahim M. Elmojtaba, Rayan M. Altayeb

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Visceral leishmaniasis (VL) is a vector-borne disease caused by the protozoa parasite of the genus leishmania. The transmission of the parasite to humans and animals occurs via the bite of adult female sandflies previously infected by biting and sucking blood of an infectious humans or animals. In this paper we use a previously proposed model, and then applied two optimal controls, namely treatment and vaccination to that model to investigate optimal strategies for controlling the spread of the disease using treatment and vaccination as the system control variables. The possible impact of using combinations of the two controls, either one at a time or two at a time on the spread of the disease is also examined. Our results provide a framework for vaccination and treatment strategies to reduce susceptible and infection individuals of VL in five years.

Keywords: visceral leishmaniasis, treatment, vaccination, optimal control, numerical simulation

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Authors: Y. Pilehvar-Soltanahmadi, F. Badrzadeh, N. Zarghami, S. Jalilzadeh-Tabrizi, R. Zamani

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Herbal compounds such as curcumin which decrease telomerase and gene expression have been considered as beneficial tools for lung cancer treatment. In this article, we compared the effects of pure curcumin and curcumin-loaded NIPAAm-MAA nanoparticles on telomerase and PinX1 gene expression in a lung cancer cell line. A tetrazolium-based assay was used for determination of cytotoxic effects of curcumin on the Calu-6 lung cancer cell line and telomerase and pinX1 gene expression was measured with real-time PCR. MTT assay showed that Curcumin-loaded NIPAAm-MAA inhibited the growth of the Calu-6 lung cancer cell line in a time and dose-dependent manner. Our q-PCR results showed that the expression of telomerase gene was effectively reduced as the concentration of curcumin-loaded NIPAAm-MAA increased while expression of the PinX1 gene became elevated. The results showed that curcumin loaded NIPAAm-MAA exerted cytotoxic effects on the Calu-6 cell line through down-regulation of telomerase and stimulation of pinX1 gene expression. NIPPAm-MAA could be the good carrier for such kinds of hydrophobic agent.

Keywords: curcumin, NIPAAm-MAA, PinX1, telomerase, lung cancer cells

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Authors: Mahdiar Hosseighadiry, Farnaz Fotovatikhah, Razali Ismail, Mohsen Khaledian, Mehdi Saeidemanesh

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In this paper, a new low-power high-performance full adder is presented based on a new design method. The proposed method relies on pass gate design and provides full-swing circuits with minimum number of transistors. The method has been applied on SUM, COUT and XOR-XNOR modules resulting on rail-to-rail intermediate and output signals with no feedback transistors. The presented full adder cell has been simulated in 45 and 32 nm CMOS technologies using HSPICE considering parasitic capacitance and compared to several well-known designs from literature. In addition, the proposed cell has been extensively evaluated with different output loads, supply voltages, temperatures, threshold voltages, and operating frequencies. Results show that it functions properly under all mentioned conditions and exhibits less PDP compared to other design styles.

Keywords: full adders, low-power, high-performance, VLSI design

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Authors: Alan Ruiz-Padilla, Brando Villalobos-Villalobos, Yeniley Ruiz-Noa, Claudia Mendoza-Macías, Claudia Palafox-Sánchez, Miguel Marín-Rosales, Álvaro Cruz, Rubén Rangel-Salazar

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Introduction: In patients with rheumatoid arthritis, resistance or poor response to disease modifying antirheumatic drugs (DMARD) may be a reflection of the increase in g-P. The expression of g-P may be important in mediating the effluence of DMARD from the cell. In addition, P-glycoprotein is involved in the transport of cytokines, IL-1, IL-2 and IL-4, from normal lymphocytes activated to the surrounding extracellular matrix, thus influencing the activity of RA. The involvement of P-glycoprotein in the transmembrane transport of cytokines can serve as a modulator of the efficacy of DMARD. It was shown that a number of lymphocytes with glycoprotein P activity is increased in patients with RA; therefore, P-glycoprotein expression could be related to the activity of RA and could be a predictor of poor response to therapy. Objective: To evaluate in RA patients, if the G2677T/A MDR1 polymorphisms is associated with differences in the rate of therapeutic response to disease-modifying antirheumatic agents in patients with rheumatoid arthritis. Material and Methods: A prospective cohort study was conducted. Fifty seven patients with RA were included. They had an active disease according to DAS-28 (score >3.2). We excluded patients receiving biological agents. All the patients were followed during 6 months in order to identify the rate of therapeutic response according to the American College of Rheumatology (ACR) criteria. At the baseline peripheral blood samples were taken in order to identify the G2677T/A MDR1 polymorphisms using PCR- Specific allele. The fragment was identified by electrophoresis in polyacrylamide gels stained with ethidium bromide. For statistical analysis, the genotypic and allelic frequencies of MDR1 gene polymorphism between responders and non-responders were determined. Chi-square tests as well as, relative risks with 95% confidence intervals (95%CI) were computed to identify differences in the risk for achieving therapeutic response. Results: RA patients had a mean age of 47.33 ± 12.52 years, 87.7% were women with a mean for DAS-28 score of 6.45 ± 1.12. At the 6 months, the rate of therapeutic response was 68.7 %. The observed genotype frequencies were: for G/G 40%, T/T 32%, A/A 19%, G/T 7% and for A/A genotype 2%. Patients with G allele developed at 6 months of treatment, higher rate for therapeutic response assessed by ACR20 compared to patients with others alleles (p=0.039). Conclusions: Patients with G allele of the - G2677T/A MDR1 polymorphisms had a higher rate of therapeutic response at 6 months with DMARD. These preliminary data support the requirement for a deep evaluation of these and other genotypes as factors that may influence the therapeutic response in RA.

Keywords: pharmacogenetics, MDR1, P-glycoprotein, therapeutic response, rheumatoid arthritis

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Authors: Piyush Samant, Ravinder Agarwal

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Complementary and Alternative Medicine (CAM) techniques are quite popular and effective for chronic diseases. Iridology is more than 150 years old CAM technique which analyzes the patterns, tissue weakness, color, shape, structure, etc. for disease diagnosis. The objective of this paper is to validate the use of iridology for the diagnosis of the diabetes. The suggested model was applied in a systemic disease with ocular effects. 200 subject data of 100 each diabetic and non-diabetic were evaluated. Complete procedure was kept very simple and free from the involvement of any iridologist. From the normalized iris, the region of interest was cropped. All 63 features were extracted using statistical, texture analysis, and two-dimensional discrete wavelet transformation. A comparison of accuracies of six different classifiers has been presented. The result shows 89.66% accuracy by the random forest classifier.

Keywords: complementary and alternative medicine, classification, iridology, iris, feature extraction, disease prediction

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Authors: B. Gonzalez-Yebra, H. Barajas, P. Palomares, M. Hernandez, O. Torres, M. Ayala, A. L. González, G. Vazquez-Ortiz, M. L. Guzman

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Leukemia arises by molecular alterations of the normal hematopoietic stem cell (HSC) transforming it into a leukemic stem cell (LSC) with high cell proliferation, self-renewal, and cell differentiation. Chronic myeloid leukemia (CML) originates from an LSC-leading to elevated proliferation of myeloid cells and acute lymphoblastic leukemia (ALL) originates from an LSC development leading to elevated proliferation of lymphoid cells. In both cases, LSC can be identified by multicolor flow cytometry using several antibodies. However, to date, LSC levels in peripheral blood (PB) are not established well enough in ALL and CML patients. On the other hand, the detection of the minimal residue disease (MRD) in leukemia is mainly based on the identification of the mRNA bcr-abl gene in CML patients and some other genes in ALL patients. There is no a properly biomarker to detect MDR in both types of leukemia. The objective of this study was to determine mRNA bcr-abl and the percentage of LSC in peripheral blood of patients with CML and ALL and identify a possible association between the amount of LSC in PB and clinical data. We included in this study 19 patients with Leukemia. A PB sample was collected per patient and leukocytes were obtained by Ficoll gradient. The immunophenotype for LSC CD34+ was done by flow cytometry analysis with CD33, CD2, CD14, CD16, CD64, HLA-DR, CD13, CD15, CD19, CD10, CD20, CD34, CD38, CD71, CD90, CD117, CD123 monoclonal antibodies. In addition, to identify the presence of the mRNA bcr-abl by RT-PCR, the RNA was isolated using TRIZOL reagent. Molecular (presence of mRNA bcr-abl and LSC CD34+) and clinical results were analyzed with descriptive statistics and a multiple regression analysis was performed to determine statistically significant association. In total, 19 patients (8 patients with ALL and 11 patients with CML) were analyzed, 9 patients with de novo leukemia (ALL = 6 and CML = 3) and 10 under treatment (ALL = 5 and CML = 5). The overall frequency of mRNA bcr-abl was 31% (6/19), and it was negative in ALL patients and positive in 80% in CML patients. On the other hand, LSC was determined in 16/19 leukemia patients (%LSC= 0.02-17.3). The Novo patients had higher percentage of LSC (0.26 to 17.3%) than patients under treatment (0 to 5.93%). The amount of LSC was significantly associated with the amount of LSC were: absence of treatment, the absence of splenomegaly, and a lower number of leukocytes, negative association for the clinical variables age, sex, blasts, and mRNA bcr-abl. In conclusion, patients with de novo leukemia had a higher percentage of circulating LSC than patients under treatment, and it was associated with clinical parameters as lack of treatment, absence of splenomegaly and a lower number of leukocytes. The mRNA bcr-abl detection was only possible in the series of patients with CML, and molecular detection of LSC could be identified in the peripheral blood of all leukemia patients, we believe the identification of circulating LSC may be used as biomarker for the detection of the MRD in leukemia patients.

Keywords: stem cells, leukemia, biomarkers, flow cytometry

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Authors: S. Rodosik, J. P. Poirot-Crouvezier, Y. Bultel

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With the expansion of the hydrogen economy, Proton Exchange Membrane Fuel Cell (PEMFC) systems are often presented as promising energy converters suitable for transport applications. However, reaching a durability of 5000 h recommended by the U.S. Department of Energy and decreasing system cost are still major hurdles to their development. In order to increase the system efficiency and simplify the system without affecting the fuel cell lifetime, an architecture called alternative fuel feeding has been developed. It consists in a fuel cell stack divided into two parts, alternatively fed, implemented on a 5-kW system for real scale testing. The operation strategy can be considered close to Dead End Anode (DEA) with specific modifications to avoid water and nitrogen accumulation in the cells. The two half-stacks are connected in series to enable each stack to be alternatively fed. Water and nitrogen accumulated can be shifted from one half-stack to the other one according to the alternative feeding frequency. Thanks to the homogenization of water vapor along the stack, water management was improved. The operating conditions obtained at system scale are close to recirculation without the need of a pump or an ejector. In a first part, a performance comparison with the DEA strategy has been performed. At high temperature and low pressure (80°C, 1.2 bar), performance of alternative fuel feeding was higher, and the system efficiency increased. In a second part, in order to highlight the benefits of the architecture on the fuel cell lifetime, two durability tests, lasting up to 1000h, have been conducted. A test on the 5-kW system has been compared to a reference test performed on a test bench with a shorter stack, conducted with well-controlled operating parameters and flow-through hydrogen strategy. The durability test is based upon the Fuel Cell Dynamic Load Cycle (FC-DLC) protocol but adapted to the system limitations: without OCV steps and a maximum current density of 0.4 A/cm². In situ local measurements with a segmented S++® plate performed all along the tests, showed a more homogeneous distribution of the current density with alternative fuel feeding than in flow-through strategy. Tests performed in this work enabled the understanding of this architecture advantages and drawbacks. Alternative fuel feeding architecture appeared to be a promising solution to ensure the humidification function at the anode side with a simplified fuel cell system.

Keywords: automotive conditions, durability, fuel cell system, proton exchange membrane fuel cell, stack architecture

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Authors: G. Tamilpavai, C. Vishnuppriya

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Bioinformatics is an active research area which combines biological matter as well as computer science research. The longest common subsequence (LCSS) is one of the major challenges in various bioinformatics applications. The computation of the LCSS plays a vital role in biomedicine and also it is an essential task in DNA sequence analysis in genetics. It includes wide range of disease diagnosing steps. The objective of this proposed system is to find the longest common subsequence which presents in a normal and various disease affected human DNA sequence using Self Organizing Map (SOM) and LCSS. The human DNA sequence is collected from National Center for Biotechnology Information (NCBI) database. Initially, the human DNA sequence is separated as k-mer using k-mer separation rule. Mean and median values are calculated from each separated k-mer. These calculated values are fed as input to the Self Organizing Map for the purpose of clustering. Then obtained clusters are given to the Longest Common Sub Sequence (LCSS) algorithm for finding common subsequence which presents in every clusters. It returns nx(n-1)/2 subsequence for each cluster where n is number of k-mer in a specific cluster. Experimental outcomes of this proposed system produce the possible number of longest common subsequence of normal and disease affected DNA data. Thus the proposed system will be a good initiative aid for finding disease causing sequence. Finally, performance analysis is carried out for different DNA sequences. The obtained values show that the retrieval of LCSS is done in a shorter time than the existing system.

Keywords: clustering, k-mers, longest common subsequence, SOM

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Authors: Ilirian Laçi, Alketa Spahiu

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Modality of treatment in hepatocellular carcinoma (HCC) patients depends on the stage of the disease. The Barcelona Clinic Liver Cancer Classification (BCLC) is the preferred staging system. There are many patients initially present with intermediate-stage disease. For these patients, transarterial chemoembolization (TACE) is the treatment of choice. The differences in individual factors that are not captured by the BCLC framework, such as the tumor growth pattern, degree of hypervascularity, and vascular supply, complicate further evaluation of these patients. Because of these differences, not all patients benefit equally from TACE. Several tools have been devised to aid the decision-making process, which have shown promising initial results but have failed external evaluation and have not been translated to the clinic aspects. Criteria for treatment decisions in daily clinical practice are needed in all stages of the disease.

Keywords: hepatocellular carcinoma, transarterial chemoembolization, TACE, liver

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Authors: Omar Khan, Shana Krstevska, Edwin George, Veronica Gorden, Fen Bao, Christina Caon, NP-C, Carla Santiago, Imad Zak, Navid Seraji-Bozorgzad

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Objective: To quantify cellular injury in the substantia nigra (SN) in patients with Parkinson's disease (PD) and to examine the effect of rasagiline of tissue injury in the SN in patients with PD. Background: N-acetylaspartate (NAA) quantified with MRS is a reliable marker of neuronal metabolic function. Fractional anisotropy (FA) and mean diffusivity (MD) obtained with DTI, characterize tissue alignment and integrity. Rasagline, has been shown to exert anti-apototic effect. We applied these advanced MRI techniques to examine: (i) the effect of rasagiline on cellular injury and metabolism in patients with early PD, and (ii) longitudinal changes seen over time in PD. Methods: We conducted a prospective longitudinal study in patients with mild PD, naive to dopaminergic treatment. The imaging protocol included multi-voxel proton-MRS and DTI of the SN, acquired on a 3T scanner. Scans were performed at baseline and month 3, during which the patient was on no treatment. At that point, rasagiline 1 mg orally daily was initiated and MRI scans are were obtained at 6 and 12 months after starting rasagiline. The primary objective was to compare changes during the 3-month period of “no treatment” to the changes observed “on treatment” with rasagiline at month 12. Age-matched healthy controls were also imaged. Image analysis was performed blinded to treatment allocation and period. Results: 25 patients were enrolled in this study. Compared to the period of “no treatment”, there was significant increase in the NAA “on treatment” period (-3.04 % vs +10.95 %, p= 0.0006). Compared to the period of “no treatment”, there was significant increase in following 12 month in the FA “on treatment” (-4.8% vs +15.3%, p<0.0001). The MD increased during “no treatment” and decreased in “on treatment” (+2.8% vs -7.5%, p=0.0056). Further analysis and clinical correlation are ongoing. Conclusions: Advanced MRI techniques quantifying cellular injury in the SN in PD is a feasible approach to investigate dopaminergic neuronal injury and could be developed as an outcome in exploratory studies. Rasagiline appears to have a stabilizing effect on dopaminergic cell loss and metabolism in the SN in PD, that warrants further investigation in long-term studies.

Keywords: substantia nigra, Parkinson's disease, MRI, neuronal loss, biomarker

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Authors: Alejandra Betancur Sánchez, Carmen Elena Zapata Sánchez, Juan Bautista López Ortiz

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Adverse effects and increased air pollution has raised concerns about regulatory policies and has fostered the development of new air quality standards; this is due to the complexity of the composition and the poorly understood reactions in the atmospheric environment. Toxic compounds act as environmental agents having various effects, from irritation to death of cells and tissues. A toxic agent is defined an adverse response in a biological system. There is a particular class that produces some kind of alteration in the genetic material or associated components, so they are recognized as genotoxic agents. Within cells, they interact directly or indirectly with DNA, causing mutations or interfere with some enzymatic repair processes or in the genesis or polymerization of proteinaceous material involved in chromosome segregation. An air pollutant may cause or contribute to increased mortality or serious illness and even pose a potential danger to human health. The aim of this study was to evaluate the effect on the viability and the genotoxic potential on the cell lines CHO-K1 and Jurkat and peripheral blood of particulate matter PM T lymphocytes 2.5 obtained from filters collected three monitoring stations network air quality Aburrá Valley. Tests, reduction of MTT, trypan blue, NRU, comet assay, sister chromatid exchange (SCE) and chromosomal aberrations allowed evidence reduction in cell viability in cell lines CHO-K1 and Jurkat and damage to the DNA from cell line CHOK1, however, no significant effects were observed in the number of SCEs and chromosomal aberrations. The results suggest that PM2.5 material has genotoxic potential and can induce cancer development, as has been suggested in other studies.

Keywords: PM2.5, cell line Jurkat, cell line CHO-K1, cytotoxicity, genotoxicity

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Authors: Annisa Ulfah Pristya, Andi Setiawan

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Electricity is the primary requirement today's world, including Indonesia. This is because electricity is a source of electrical energy that is flexible to use. Fossil energy sources are the major energy source that is used as a source of energy power plants. Unfortunately, this conversion process impacts on the depletion of fossil fuel reserves and causes an increase in the amount of CO2 in the atmosphere, disrupting health, ozone depletion, and the greenhouse effect. Solutions have been applied are solar cells, ocean wave power, the wind, water, and so forth. However, low efficiency and complicated treatment led to most people and industry in Indonesia still using fossil fuels. Referring to this Fuel Cell was developed. Fuel Cells are electrochemical technology that continuously converts chemical energy into electrical energy for the fuel and oxidizer are the efficiency is considerably higher than the previous natural source of electrical energy, which is 40-60%. However, Fuel Cells still have some weaknesses in terms of the use of an expensive platinum catalyst which is limited and not environmentally friendly. Because of it, required the simultaneous source of electrical energy and environmentally friendly. On the other hand, Indonesia is a rich country in marine sediments and organic content that is never exhausted. Stacking the organic component can be an alternative energy source continued development of fuel cell is A Microbial Fuel Cell. Microbial Fuel Cells (MFC) is a tool that uses bacteria to generate electricity from organic and non-organic compounds. MFC same tools as usual fuel cell composed of an anode, cathode and electrolyte. Its main advantage is the catalyst in the microbial fuel cell is a microorganism and working conditions carried out in neutral solution, low temperatures, and environmentally friendly than previous fuel cells (Chemistry Fuel Cell). However, when compared to Chemistry Fuel Cell, MFC only have an efficiency of 40%. Therefore, the authors provide a solution in the form of Nano-MFC (Nano Microbial Fuel Cell): Utilization of Carbon Nano Tube to Increase Efficiency of Microbial Fuel Cell Power as an Effective, Efficient and Environmentally Friendly Alternative Energy Source. Nano-MFC has the advantage of an effective, high efficiency, cheap and environmental friendly. Related stakeholders that helped are government ministers, especially Energy Minister, the Institute for Research, as well as the industry as a production executive facilitator. strategic steps undertaken to achieve that begin from conduct preliminary research, then lab scale testing, and dissemination and build cooperation with related parties (MOU), conduct last research and its applications in the field, then do the licensing and production of Nano-MFC on an industrial scale and publications to the public.

Keywords: CNT, efficiency, electric, microorganisms, sediment

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Authors: Akudo Ejelonu, Sarah Willig, J. Anthony Sauder, Heather Murphy, Frances Shofer

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Background: The high prevalence of diarrheal diseases in the village of Tzununá, Guatemala is linked to lack of sanitation facilities and handwashing practices. Diarrheal diseases are preventable and improved access to latrines, hygiene education and clean water may improve sanitation by reducing the spread of disease. Objective: Between May 2015-January 2017, the University of Pennsylvania Chapter of Engineers Without Border (PennEWB) and local partners designed an intervention to reduce diarrheal disease by building pour flush latrines in 50 individual households and providing education on the importance of handwashing practice. Design/Methods: Through convenient sampling, we surveyed 45 households to evaluate the community’s knowledge of diarrheal disease, handwashing practices, and maintenance of the latrines. Results: 92% of the study participants experienced decrease of new cases of diarrheal disease after receiving a latrine. Only 11% washed their hands after defecating in the latrine. There was gap in understanding the health outcome of latrine sanitation and handwashing education. The respondents did not connect the reduction of diarrheal disease with latrine use and maintenance. Instead, they associated their motivation for latrine use with aesthetics, proximity to their home, ease and comfort, and reduction of shame. We recommend that PennEWB adopt UNICEF or WHO education on hand washing practice. Conclusion: Social interaction and social pressure drove the household use of latrines. The latrines are being valued and cleaned. The education that the residents received did not target norms and behaviors. Latrines could be used to create a new social norm that supports behavioral change.

Keywords: diarrheal disease, latrine, open defecation, water, sanitation and hygiene

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Authors: Seyhan Karaçavuş, Bülent Yılmaz, Ömer Kayaaltı, Semra İçer, Arzu Taşdemir, Oğuzhan Ayyıldız, Kübra Eset, Eser Kaya

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In this study, our goal was to perform tumor staging and subtype determination automatically using different texture analysis approaches for a very common cancer type, i.e., non-small cell lung carcinoma (NSCLC). Especially, we introduced a texture analysis approach, called Law’s texture filter, to be used in this context for the first time. The 18F-FDG PET images of 42 patients with NSCLC were evaluated. The number of patients for each tumor stage, i.e., I-II, III or IV, was 14. The patients had ~45% adenocarcinoma (ADC) and ~55% squamous cell carcinoma (SqCCs). MATLAB technical computing language was employed in the extraction of 51 features by using first order statistics (FOS), gray-level co-occurrence matrix (GLCM), gray-level run-length matrix (GLRLM), and Laws’ texture filters. The feature selection method employed was the sequential forward selection (SFS). Selected textural features were used in the automatic classification by k-nearest neighbors (k-NN) and support vector machines (SVM). In the automatic classification of tumor stage, the accuracy was approximately 59.5% with k-NN classifier (k=3) and 69% with SVM (with one versus one paradigm), using 5 features. In the automatic classification of tumor subtype, the accuracy was around 92.7% with SVM one vs. one. Texture analysis of FDG-PET images might be used, in addition to metabolic parameters as an objective tool to assess tumor histopathological characteristics and in automatic classification of tumor stage and subtype.

Keywords: cancer stage, cancer cell type, non-small cell lung carcinoma, PET, texture analysis

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Authors: Maha Soltan, Amal Z. Hassan, Howaida I. Abd-Alla, Atef G. Hanna

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Two naturally known cardenolides; acovenoside A and acobioside A were isolated from the Egyptian cultivar; Acokanthera spectabilis leaves. It is an ornamental and poisonous plant that has been traditionally claimed for their medicinal properties against infectious microbes, killing worms and curing some inflammations at little amounts. We examined the growth inhibition effects of both cardenolides against four types of human cancer cell lines using Sulphorhodamine B assay. In addition, the clonogenic assay was also performed for testing the growth inhibiting power of the isolated compounds. An in vitro mechanistic investigation was further accomplished against hepatocellular carcinoma HepG2 cell line. Microscopic examination, colorimetric ELISA and flow cytometry techniques were our tools of proving at least part of the anticancer pathway of the tested compounds. Both compounds were able to inhibit the growth of 4 human cancer cell lines at less than 100 nM. In addition, they were able to activate the executioner Caspase-3 and apoptosis was then induced as a consequence of cell growth arrest at G2/M. An attention must be payed to those bioactive agents particularly when giving their activity against cancer cells at considerable small values while presenting safe therapeutic margins as indicated by literature.

Keywords: anticancer, cardenolides, Caspase-3, apoptosis

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Authors: Nurul Hamirah Kamsani, Mohd Hamim Rajikin, Nor Ashikin Mohamed Noor Khan, Sharaniza Abdul Rahim

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Cytoskeletal structures, in particular actin and tubulin, provide a fundamental framework in all cells, including embryos. Under influence of nicotine, the cytoskeletal organization may be subjected to oxidative stress (OS) insult and cause alteration. Tocotrienol-rich fraction (TRF) is proven to enhance fertility better than the other sub-group of Vitamin E, tocopherols (TCPs). The objective of this study was to evaluate the effects of TRF on 1) actin and tubulin of 2- and 8-cell murine embryos and 2) the regulation of reactive oxygen species (ROS)-scavenging enzymes; induced by nicotine. Twenty four female Balb/C were subjected to either subcutaneous (sc) injection of 0.9% NaCl; sc injection of 3.0 mg/kg bw/day nicotine; sc injection of 3.0 mg/kg bw/day nicotine + oral gavage (OG) of 60 mg/kg bw/day TRF; or OG of 60 mg/kg bw/day TRF for 7 consecutive days. After superovulation and mating, animals were euthanized. 2-cell developing embryos were retrieved. 50% of the retrieved embryos were visualized under confocal laser staining microscopy (CLSM) for alterations of actin and tubulin. The remaining amount of embryos was cultured in vitro until 8-cell stage followed by CLSM visualization. Blood plasma was subjected to OS assays. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined and analysed accordingly. At both 2- and 8-cell developing stages, actin intensities were significantly reduced in the nicotine group (p<0.001). After the intervention, actin intensity was significantly increased compared to that of the nicotine group (p<0.001). The same trend was seen in tubulin at both cell stages. TRF has minimized the deleterious effects of nicotine in actin and tubulin of both 2- and 8-cell developmental stages during pre-implantation embryonic development in mice in vitro. Levels of endogenous anti-oxidative enzymes were sustained close to control accompanied by decreased levels of OS biomarker.

Keywords: actin, nicotine, pre-implantation embryos, tocotrienol rich fraction, tubulin

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Authors: Awet Araya

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Cochliobolus sativus ((anamorphic stage: Bipolaris sorokiniana (synonyms: Helminthosporium sorokinianum, Drechslera sorokiniana, and Helminthosporium sativum)) is an important pathogen of cereal crops. Many other grass species are also hosts for this fungus. Yield losses have been reported from many regions, especially where barley and wheat are commercially cultivated. The fungus has a worldwide distribution. The pathogen causes root rot, seedling blight, spot blotch, head blight, and black point. Environmental conditions affect disease development. Most of the time, fungus survives as mycelia and conidia. Pseudothecium of the fungus is not commonly encountered and probably not important in the epidemiology of the disease. The fungus can be in seed, soil, or in plant parts. Crop rotation, proper fertilization, reducing other stress factors, fungicide treatments, and resistant cultivars may be used for the control of the disease.

Keywords: Cochliobolus sativus, barley, cultivars, root rot

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Authors: Samira B. R. Prado, Paulo R. Melfi, Beatriz T. Minguzzi, João P. Fabi

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Fruit softening is the main change that occurs during papaya (Carica papaya L.) ripening. It is characterized by the depolymerization of cell wall polysaccharides, especially the pectic fractions, which causes cell wall disassembling. However, it is uncertain how the modification of the two main pectin polysaccharides fractions (water-soluble – WSF, and oxalate-soluble fractions - OSF) accounts for fruit softening. The aim of this work was to correlate molecular weight changes of WSF and OSF with the gene expression of pectin-solubilizing enzymes (pectinases) during papaya ripening. Papaya fruits obtained from a producer were harvest and storage under specific conditions. The fruits were divided in five groups according to days after harvesting. Cell walls from all groups of papaya pulp were isolated and fractionated (WSF and OSF). Expression profiles of pectinase genes were achieved according to the MIQE guidelines (Minimum Information for publication of Quantitative real-time PCR Experiments). The results showed an increased yield and a decreased molecular weight throughout ripening for WSF and OSF. Gene expression data support that papaya softening is achieved by polygalacturonases (PGs) up-regulation, in which their actions might have been facilitated by the constant action of pectinesterases (PMEs). Moreover, BGAL1 gene was up-regulated during ripening with a simultaneous galactose release, suggesting that galactosidases (GALs) could also account for pulp softening. The data suggest that a solubilization of galacturonans and a depolymerization of cell wall components were caused mainly by the action of PGs and GALs.

Keywords: carica papaya, fruit ripening, galactosidases, plant cell wall, polygalacturonases

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Authors: Chandralekha Ashangari, Amer Suleman

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Background and Purpose: The Postural Orthostatic Tachycardia Syndrome (POTS) affects primarily young women. POTS is a form of dysautonomia that is estimated to impact between 1,000,000 and 3,000,000 Americans, and millions more around the world. POTS is a form of orthostatic intolerance that is associated with many Gastrointestinal disturbances. The aim of this study is to determine the Gastrointestinal disturbances in Postural Orthostatic Tachycardia Syndrome (POTS) patients.2. Methods: 249 patients referred to our clinic from January to November with POTS. Reviewed the medical records of 249 POTS patients and gastrointestinal symptoms. Results: however out of 249 patients, 226 patients are female (90.76%; average age 32.69), 23 patients are male (9.24%; average age 27.91) Data analysis: Out of 249 patients 189 patients (76%) had vomiting or nausea, 150 patients (60%) had irritable bowel syndrome, 128 patients (51%) had bloating, 125 patients (50%) had constipation , 80 patients (32%) had abdominal pain, 56 patients (22%) had delayed gastric emptying, 24 patients (10%) had lactose intolerance, 8 patients (3%) had Gastroesophageal reflux disease, 5 patients (2%) had Iron deficiency anemia, 6 patients (2%) had Peptic ulcer disease, 4 patients (2%) had Celiac Disease. Conclusion: Patients with POTS have a very high prevalence of gastrointestinal symptoms however the majority of abnormalities appear to be motility related. Motility testing should be performed be performed in POTS patients. The diagnostic yield of endoscopic procedures appears to be low.

Keywords: gastrointestinal disturbances, Postural Orthostatic Tachycardia Syndrome (POTS), celiac disease, POTS patients

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Authors: Vidhula Ahire, Amit Kumar, K. P. Mishra, Gauri Kulkarni

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Herbal polyphenols have gained significance because of their increasing promise in prevention and treatment of cancer. Therefore, development of a dietary compound as an effective radiosensitizer and a radioprotector is highly warranted for cervical cancer patients undergoing therapy. This study describes the cytotoxic effects of the flavonoid, ellagic acid (EA) when administered either alone or in combination with gamma radiation on cervical cancer HeLa cells in vitro. Apoptotic index and proliferation were measured by using trypan blue assay. Reproductive cell death was analyzed by clonogenic assay. Propidium iodide staining for flowcytometry was performed to analyze cell cycle modulation. Nuclear and mitochondrial changes were studied with specific dyes. DNA repair kinetics was analyzed by immunofluorescence assay. Evaluation and comparison of EA effects were performed with other clinically used breast cancer drugs. When tumor cells were exposed to 2 and 4 Gy of irradiation in presence of EA (10 μM), it yielded a synergistic cytotoxic effect on cervical cancer cells whereas in NIH3T3 cells it reversed the injury caused by irradiation and abetted in the regaining of normal healthy cells. At 24h ~25foci/cell was observed and 2.6 fold decrease in the mitochondrial membrane potential. Up to 40% cell were arrested in the G1 phase and 20-36% cells exhibited apoptosis. Our results demonstrate the role of increased apoptosis and cell cycle modulation in the mechanism of EA mediated radiosensitization of cervical cancer cells and thus advocating EA as an adjuvant for preclinical trials in cancer chemo- radiotherapy.

Keywords: cervical cancer, ellagic acid, sensitization, radiation therapy

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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: Shi-xia Xu, Zai-wen Zhang, Ru-xue Chen, Shan Zhou, Xiang-feng Tang

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Objective: The clinical influence of HLA-DPB1 mismatches on clinical outcome of HSCT is less clear. This is the first meta-analysis to study the HLA-DPB1 matching statues on clinical outcomes after unrelated donor HSCT. Methods: We searched the CIBMTR, Cochrane Central Register of Controlled Trials (CENTRAL) and related databases (1995.01–2017.06) for all relevant articles. Comparative studies were used to investigate the HLA-DPB1 loci mismatches on clinical outcomes after unrelated donor HSCT, such as the disease-free survival (DFS), overall survival, GVHD, relapse, and transplant-related mortality (TRM). We performed meta-analysis using Review Manager 5.2 software and funnel plot to assess the bias. Results: At first, 1246 articles were retrieved, and 18 studies totaling 26368 patients analyzed. Pooled comparisons of studies found that the HLA-DPB1 mismatched group had a lower rate of DFS than the DPB1-matched group, and lower OS in non-T cell depleted transplantation. The DPB1 mismatched group has a higher incidence of aGVHD and more severe ( ≥ III degree) aGvHD, lower rate of relapse and higher TRM. Moreover, compared with 1-antigen mismatch, 2-antigen mismatched led to a higher risk of TRM and lower relapse rate. Conclusions: This meta-analysis indicated HLA-DPB1 has important influence on survival and transplant-related complications during unrelated donor HSCT and HLA-DPB1 donor selection strategies have been proposed based on a personalized algorithm.

Keywords: human leukocyte antigen, DPB1, transplant, meta-analysis, outcome

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Authors: Nisha Singh, Neeru Adlakha

Abstract:

Calcium signalling is one of the most important intracellular signalling mechanisms. A lot of approaches and investigators have been made in the study of calcium signalling in various cells to understand its mechanisms over recent decades. However, most of existing investigators have mainly focussed on the study of calcium signalling in various cells without paying attention to the dependence of calcium signalling on other chemical ions like inositol-1; 4; 5 triphosphate ions, etc. Some models for the independent study of calcium signalling and inositol-1; 4; 5 triphosphate signalling in various cells are present but very little attention has been paid by the researchers to study the interdependence of these two signalling processes in a cell. In this paper, we propose a coupled mathematical model to understand the interdependence of inositol-1; 4; 5 triphosphate dynamics and calcium dynamics in a myocyte cell. Such studies will provide the deeper understanding of various factors involved in calcium signalling in myocytes, which may be of great use to biomedical scientists for various medical applications.

Keywords: calcium signalling, coupling, finite difference method, inositol 1, 4, 5-triphosphate

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Authors: A. Uludağ, F. G. Tufekci, N. Ceviz

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Aim: The research has been carried out in order to evaluate caregiver burden, life satisfaction and received social support level of the parents whose children have congenital heart disease; to examine the relationship between the social supports received by them and caregiver burden and life satisfaction. Material and Method: The research which is descriptive and which is searching a relationship has been carried out between the dates June 7, 2012- June 30, 2014, in Erzurum Ataturk University Research and Application Hospital, Department of Pediatrics and Children Cardiology Polyclinic. In the research, it was collaborated with the parents (N = 157) who accepted to participate in, of children who were between the ages of 3 months- 12 years. While gathering the data, a questionnaire, Zarit Caregiver Burden, Life Satisfaction and Social Support Scales have been used. The statistics of the data acquired has been produced by using percentage distribution, mean, and variance and correlation analysis. Ethical principles are followed in the research. Results: In the research, caregiver burden, life satisfaction and social support level received from family (p < 0.05), have been determined higher in the parents whose children have serious congenital heart disease than that of parents whose children have slight disease and social support received from friends has been found lower. It has been determined that there is a strong relation (p < 0.001) through negative direction between both social support levels and caregiver burden of parents; and that there is a strong relation (p < 0.001) through positive direction between both support levels and life satisfaction. Conclusion: That Social Support is in a strong relation with Caregiver Burden through a negative direction and a strong relation with Life Satisfaction through positive direction in parents of all the children who have congenital heart disease requires social support systems to be reinforced. Parents can be led or guided so as to prompt social support systems more.

Keywords: congenital heart disease, child, parents, caregiver burden, life satisfaction, social support

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Authors: Fahad Almehmadi, Abdullah Alrajhi, Bader K. Alaslab, Abdullah A. Al Qurashi, Hattan A. Hassani

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Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) is an uncommon, inheritable cardiac disorder characterized by the progressive substitution of cardiac myocytes by fibro-fatty tissues. This pathologic substitution predisposes patients to ventricular arrhythmias and right ventricular failure. The underlying genetic defect predominantly involves genes encoding for desmosome proteins, particularly plakophilin-2 (PKP2). These aberrations lead to impaired cell adhesion, heightening the susceptibility to fibrofatty scarring under conditions of mechanical stress. Primarily, ARVD/C affects the right ventricle, but it can also compromise the left ventricle, potentially leading to biventricular heart failure. Clinical presentations can vary, spanning from asymptomatic individuals to those experiencing palpitations, syncopal episodes, and, in severe instances, sudden cardiac death. The establishment of a diagnostic criterion specifically tailored for ARVD/C significantly aids in its accurate diagnosis. Nevertheless, the task of early diagnosis is complicated by the disease's frequently asymptomatic initial stages, and the overall rarity of ARVD/C cases reported globally. In some cases, as exemplified by the adult female patient in this report, the disease may advance to terminal stages, rendering therapies like Ventricular Tachycardia (VT) ablation ineffective. This case underlines the necessity for increased awareness and understanding of ARVD/C to aid in its early detection and management. Through such efforts, we aim to decrease morbidity and mortality associated with this challenging cardiac disorder.

Keywords: ARVD/C, cardiology, interventional cardiology, cardiac electrophysiology

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Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

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Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

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Authors: Yasser A. Ahmed, Juleen M Dickson, Evan S. Krystofiak, Julie A. Oliver

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Cancer cells urgently need folate to support their rapid division. Folate receptors (FR) are over-expressed on a wide range of tumor cells, including breast cancer cells. FR are distributed over the entire surface of cancer cells, but are polarized to the apical surface of normal cells. Targeting of cancer cells using specific surface molecules such as folate receptors may be one of the strategies used to kill cancer cells without hurting the neighing normal cells. The aim of the current study was to try a method of SEM detecting FR in a murine breast cancer cell model (4T1 cells) using secondary antibody conjugated to gold or gold-coated magnetite nanoparticles. 4T1 cells were suspended in RPMI medium witth FR antibody and incubated with secondary antibody for fluorescence microscopy. The cells were cultured on 30mm Thermanox coverslips for 18 hours, labeled with FR antibody then incubated with secondary antibody conjugated to gold or gold-coated magnetite nanoparticles and processed to scanning electron microscopy (SEM) analysis. The fluorescence microscopy study showed strong punctate FR expression on 4T1 cell membrane. With SEM, the labeling with gold or gold-coated magnetite conjugates showed a similar pattern. Specific labeling occurred in nanoparticle clusters, which are clearly visualized in backscattered electron images. The 4T1 tumor cell model may be useful for the development of FR-targeted tumor therapy using gold-coated magnetite nano-particles.

Keywords: cancer cell, nanoparticles, cell culture, SEM

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Authors: Dhruv J. Limaye, Hanga Galfalvy, Cheick A. Sissoko, Yung-yu Huang, Chunanning Tang, Ying Liu, Shu-Chi Hsiung, Andrew J. Dwork, Gorazd B. Rosoklija, Victoria Arango, Lewis Brown, J. John Mann, Maura Boldrini

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Memory and emotion require hippocampal cell viability and connectivity and are disrupted in major depressive disorder (MDD). Applying shotgun proteomics and stereological quantification of neural progenitor cells (NPCs), intermediate neural progenitors (INPs), and mature granule neurons (GNs), to postmortem human hippocampus, identified differentially expressed proteins (DEPs), and fewer NPCs, INPs and GNs, in untreated MDD (uMDD) compared with non-psychiatric controls (CTRL) and antidepressant-treated MDD (MDDT). DEPs lower in uMDD vs. CTRL promote mitosis, differentiation, and prevent apoptosis. DEPs higher in uMDD vs. CTRL inhibit the cell cycle, and regulate cell adhesion, neurite outgrowth, and DNA repair. DEPs lower in MDDT vs. uMDD block cell proliferation. We observe group-specific correlations between numbers of NPCs, INPs, and GNs and an abundance of proteins regulating mitosis, differentiation, and apoptosis. Altered protein expression underlies hippocampus cellular and volume loss in uMDD, supports a trophic effect of antidepressants, and offers new treatment targets.

Keywords: proteomics, hippocampus, depression, mitosis, migration, differentiation, mitochondria, apoptosis, antidepressants, human brain

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Authors: Margarida Maria Cabugueira Csutódio dos Santos, Joana Filipa Pintéus Pereira

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The way children understand the concept of health and illness influences their reaction in contexts where these concepts are present (e.g.,illness; vaccination). The recognition of the importance of children's beliefs/representations about health and disease has led to the development of models that seek to explain the development process of these concepts. In the construction of their representations, children are influenced not only by their cognitive competence but also by their life experiences. In the last 3 years, children have experienced a pandemic health crisis that has exposed them to anomalous and stressful situations. Objective: the aim of this study was (1) to identify children’s representations about disease (including symptoms, causes, control/treatment) and prevention (including health procedures and vaccines) and (2) whether COVID19 is mentioned and influences their representations. Methodology: a qualitative study in which 67 children with 7 to 10 years old (mean 8,8) participated. A semi-structured interview was used following the Bibace and Walsh model, focusing on the representation of the disease and its prevention. Results show a marked influence of the lived experience with regard to causes of the disease, disease control and treatment, and adherence to vaccination. Age-dependent differences were found with older children being able to talk about illness and contamination process and younger displaying more basic, concrete and rigid representations. Conclusions: The results of this study bring clues to the adequacy of communication with the child in the context of health and illness and discriminately in a future health pandemic crisis.

Keywords: childen, health beliefs, pediatrics, covid19, vaccines

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Authors: Daruliza Kernain, Shaharum Shamsuddin, See Too Wei Cun

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CTCF is a unique, highly conserved and ubiquitously expressed 11 zinc finger (ZF) transcriptional factor with multiple target sites. It is able to bind to various target sequences to perform different regulatory roles including promoter activation or repression, creating hormone-responsive gene silencing element, and functional block of enhancer-promoter interactions. The binding of CTCF to the essential binding site is through the combination of different ZF domain. On the other hand, BORIS for brother of the regulator of imprinted sites, which expressed only in the testis and certain cancer cell line is homology to CTCF 11 ZF domains. Since both transcriptional factors share the same ZF domains hence there is a possibility for both to bind to the same target sequences. In this study, the interaction of these two proteins to multi-functional Y-box DNA/RNA-binding factor, YB-1 was determined. The protein-protein interaction between CTCF/YB-1 and BORIS/YB-1 were discovered by Co-immuno-precipitation (CO-IP) technique through reciprocal experiment from RGBM total cell lysate. The results showed that both CTCF and BORIS were able to interact with YB-1 in Glioma RGBM cell line. To the best of our knowledge, this is the first findings demonstrating the ability of BORIS and YB-1 to form a complex in vivo.

Keywords: immunoprecipitation, CTCF/BORIS/YB-1, transcription factor, molecular medicine

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