Search results for: glycogen storage disease

Authors: Syed Dawood Md. Taimur, Md. Hasanur Rahman, Syeda Fahmida Afrin, Farzana Islam

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The concept of myocardial injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur either spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. In recent years, percutaneous coronary intervention (PCI) has become a well-established technique for the treatment of coronary artery disease. PCI improves symptoms in patients with coronary artery disease and it has been increasing the safety of procedures. However, peri- and post-procedural myocardial injury, including angiographical slow coronary flow, microvascular embolization, and elevated levels of cardiac enzyme, such as creatine kinase and troponin-T and -I, has also been reported even in elective cases. Furthermore, myocardial reperfusion injury at the beginning of myocardial reperfusion, which causes tissue damage and cardiac dysfunction, may occur in cases of the acute coronary syndrome. Because patients with myocardial injury is related to larger myocardial infarction and have a worse long-term prognosis than those without myocardial injury, it is important to prevent myocardial injury during and/or after PCI in patients with coronary artery disease. To date, many studies have demonstrated that adjunctive pharmacological treatment suppresses myocardial injury and increases coronary blood flow during PCI procedures. In this review, we highlight the usefulness of pharmacological treatment in combination with PCI in attenuating myocardial injury in patients with coronary artery disease.

Keywords: coronary artery disease, percutaneous coronary intervention, myocardial injury, pharmacology

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Authors: A. Morina, S. Ö. Muti, M. Öztürk

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Celiac disease is a chronic intestinal disease observed in individuals with gluten intolerance. In this study, our aim was to create a protein matrix to mimic the functional properties of gluten. For this purpose, rennet casein and four emulsifying salts (disodium phosphate (DSP), tetrasodium pyrophosphate (TSPP), sodium acid pyrophosphate (SAPP), and sodium hexametaphosphate (SHMP)) were investigated in gluten-free bread manufacture. Compositional, textural, and visual properties of the gluten-free bread dough and gluten-free breads were investigated by a two–level factorial experimental design with two-star points (α = 1.414) and two replicates of the center point. Manufacturing gluten-free bread with rennet casein and SHMP significantly increased the bread volume (P < 0.0001, R² = 97.8). In general, utilization of rennet casein with DSP and SAPP increased bread hardness while no difference was observed in samples manufactured with TSPP and SHMP. Except for TSPP, bread color was improved by the utilization of rennet casein and DSP, SAPP, and SHMP combinations. In conclusion, it is possible to manufacture gluten-free bread with acceptable texture and color by rennet casein and SHMP.

Keywords: celiac disease, gluten-free bread, emulsified salts, rennet casein, rice flour

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Authors: K. Kusakana

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A hybrid energy system is a combination of renewable energy sources with back up, as well as a storage system used to respond to given load energy requirements. Given that the electrical output of each renewable source is fluctuating with changes in weather conditions, and since the load demand also varies with time; one of the main attributes of hybrid systems is to be able to respond to the load demand at any time by optimally controlling each energy source, storage and back-up system. The induced optimization problem is to compute the optimal operation control of the system with the aim of minimizing operation costs while efficiently and reliably responding to the load energy requirement. Current optimization research and development on hybrid systems are mainly focusing on the sizing aspect. Thus, the aim of this paper is to report on the state-of-the-art of optimal operation control of hybrid renewable energy systems. This paper also discusses different challenges encountered, as well as future developments that can help in improving the optimal operation control of hybrid renewable energy systems.

Keywords: renewable energies, hybrid systems, optimization, operation control

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Authors: Surekha Rathod

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Sickle cell disease is a vascular disorder characterized by chronic, ongoing organ damage that is punctuated by episodes of acutely painful vascular complications.1 It is the most common genetic blood disorder in the United States, with about 2000 infants being identified through routine blood screenings annually, and an estimated 104,000-138,000 affected individuals living in the United States. Approximately 0.3%-1.3% of African American are affected by Sickle Cell Diseases (SCD).3 The aim of this paper is to present oral health status of patients with SCD. A total of 200 subjects of both sexes in the age group 18- 40 years were included in this study. The subjects were examined and the following indices were recorded • Oral hygiene index – Simplified (OHI-S). • Probing depths (PD). • Clinical Attachment Levels (CAL). • Gingival Index - Loe and Sillness. • Turesky Gillmore Glickman Modification of the Quigley Hein Plaque Index. (1970) • DMFT index. • Sickle Cell Disease Severity Index. A total of 1478 patients were screened of which 200 subjects were found to be diagnosed with SCD by electrophoresis. The study thus, included 200 subjects (111 females & 89 males) diagnosed with Sickle Cell Disease in the age group of 18-40 years. The probing pocket depths (PPD) were measured in millimeters. 36% had PPD in the range of 2-4mm, 48% had PPD in the range of 4-6mm while 16% had PPD of more than 6mm. Similar results were obtained for the Clinical Attachment Levels (CAL). 29.5 % subjects had CAL 2-4mm, 44.5% had 4-6mm & 26% had CAL 6mm & above. We can thus conclude that although oral health is not a priority for patients with SCD, it is supported by increased plaque accumulation. Because of the chronic anemic state of the patients with SCD, they should be encouraged to pay strict attention to oral hygiene instructions and practice.

Keywords: chronic, genetic, oral, sickle cell disease, vascular

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Authors: Jennifer Hunter, Francisco Ramirez, Neil A. Nedley, Thania Solorio, Christian Freed, Erica Kinjo

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People who have autoimmune disease are often at an increased risk for psychological disorders such as anxiety. Untreated psychological conditions can affect the development of disease and can affect one’s general quality of life. In this study, it was hypothesized that an educational community-based intervention would be useful in decreasing the anxiety levels of participants with autoimmune disease. Programs, 2-hours long each, were held weekly over a period of eight weeks. During every meeting, a 45-minute DVD presentation by a skilled physician was shown, a small group discussion was guided by trained facilitators, and weekly practical assignments were given to each participant. The focus of the program was to educate participants about healthy lifestyle behaviors such as exercise, nutrition, sleep hygiene, helpful thought patterns etc., and to provide a group environment in which each participant was supported. Participants were assessed pre-post program for anxiety using the Depression and Anxiety Assessment Test (registration TX 7-398-022), a validated mental health test based on DSM-5 criteria and demographics. Anxiety scores were classified according to the DSM-5 criteria into 4 categories: none (0-6), mild (7-10), moderate (11-19) or severe (20 or more). Out of the participants who participated in programs conducted in the manner explained above (n=431), the average age was 54.9 (SD 16.6) and 81.9% were female. At baseline, the mean group anxiety level was 9.4 (SD 5.4). Within the baseline group, anxiety levels were as follows: none (21.1%), mild (22.0%), moderate (27.1%) and severe (29.7%). After the program, mean group anxiety decreased to 4.7 (SD 4.0). Post-program anxiety levels were as follows: none (54.8%), mild (27.1%), moderate (12.5%), severe (5.6%). The decrease in overall anxiety levels was significant t(431)=19.3 p<.001, 95% CI [0.815, 1.041]. It was concluded that the eight-week intensive was beneficial in decreasing the anxiety levels of participants. A long-term follow-up study would be beneficial in determining how lasting such improvements are especially since autoimmune diseases are often chronic. Additionally, future studies that utilize a control group would aid in establishing whether the improvements seen are due to the use of this specific lifestyle-educational program.

Keywords: anxiety, auto-immune disease, community-based educational program, lifestyle

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Authors: Hamida Memon

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Rheumatoid arthritis (RA) is a persistent inflammation of the joints caused by an aggressive immune reaction leading to pain, stiffness, and limited function. Abatacept, a selective co-modulator, is a promising option for treatment and may have better safety profiles compared to other interventions. This meta-analysis aims at assessing the effectiveness and safety of abatacept in contrast to various RA treatments such as placebos, biological DMARDs and conventional DMARDs. The analysis assesses how abatacept influences disease activity, pain intensity and overall patient functionality. It weighs the risk factor of abatacept with other drugs such as tocilizumab, with the numbers being lower for abatacept. This meta-analysis aims at assessing the effectiveness and safety of abatacept in contrast to various RA treatments such as placebos, biological DMARDs and conventional DMARDs. The analysis assesses how abatacept influences disease activity, pain intensity and overall patient functionality. It weighs the risk factor of abatacept with other drugs such as tocilizumab, with the numbers being lower for abatacept.

Keywords: Rheumatoid arthritis, abatacept, control group, bone disease

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Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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Authors: Ali Bayram, Burak Uz, Ilhan Dolasik, Remzi Yiğiter

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The GABARAP (GABAA-receptor-associated protein) family consists of GABARAP, GABARAPL1 (GABARAP-like 1) and GABARAPL2 (GABARAP-like 2). GABARAPL1, like GABARAP, was described to interact with both GABAA receptor and tubulin, and to be involved in intracellular GABAA receptor trafficking and promoting tubulin polymerization. In addition, GABARAPL1 is thought to be involved in various physiological (autophagosome closure, regulation of circadian rhythms) and/or pathological mechanisms (cancer, neurodegeneration). Alzheimer’s disease (AD) is a progressive neuro degenerative disorder characterized with impaired cognitive functions. Disruption of the GABAergic neuro transmission as well as cholinergic and glutamatergic interactions, may also be involved in the pathogenesis of AD. GABARAPL1 presents a regulated tissue expression and is the most expressed gene among the GABARAP family members in the central nervous system. We, herein, conducted a study to investigate the GABARAPL1 mRNA expression levels in patients with AD. 50 patients with AD and 49 control patients were enrolled to the present study. Messenger RNA expression levels of GABARAPL1 were detected by real-time polymerase chain reaction. GABARAPL1 mRNA expression in AD / control patients was 0,495 (95% confidence interval: 0,404-0,607), p= 0,00000002646. Reduced activity of GABARAPL1 gene might play a role, at least partly, in the pathophysiology of AD.

Keywords: Alzheimer’s disease, GABARAPL1, mRNA expression, RT-PCR

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Authors: Matthew Omoniyi Adebola, Jude E Amadi

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Ground nut (Arachis hypogaea) is one of the most popular commercial crops in Nigeria. Its suc-cessful production has been drastically affected by early leaf spot disease caused by Mycosphae-rella arachidis Deighton. In vitro control of the pathogen by six medicinal plants (Entada afri-cana, Vitex doniana, Lawsonia inermis, Azadirachta indica, Acalypha hispida and Nuaclea lati-folia) was assessed in this study. The extracts of the plants were prepared using cold and hot wa-ter and alcohol. The pathogen was isolated from ground nut infected with early leaf spot disease. The results revealed a great significant difference (P<0.05) in yield of extracts between cold water, hot water, and alcohol extracts. A significant difference (P<0.05) was observed in percentage concentrations of the various phytochemical constituents present in the extracts. Flavonoids per-centage concentration was the highest (0.68 - 1.95%) followed by saponnin(0.09-1.53%) in N. latifolia extracts. Steroiods had the least percentage concentrations (0.00- 0.09%)followed by terpenoids(0.02–0.71%) and proanthocyannin (0.05 – 0.86%). N. latifolia extracts produced the highest percentage concentrations (0.07–1.95%) of all the phytochemicals followed by A. indi-ca(0.05–1.64%)and least concentrations were obtained in A. hispidia(0.09 – 0.87%)and V. do-niana (0.00–0.88%). The extracts inhibited spore germination and growth of M. arachidis. The inhibition by alcohol extracts was high and significantly different (P>0.05) from cold and hot water extracts. Alcohol extract of L. inermis gave 100% spore germination inhibition followed by N. latifolia and A.indica with 97.75% and 85.60% inhibition respectively. Therefore, field trials of these six medicinal plants on the control of early leaf spot disease of ground nut are rec-ommended.

Keywords: groundnut, phytochemicals, medicinal plants, extracts, inhibition

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Authors: Sunita Makchuchit, Arunporn Itharat

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Prasaprohyai, a Thai traditional medicine preparation listed in the Thai National List of Essential Medicines, is commonly used for treatment of fever and colds. Prasaprohyai preparation consists of 21 different plants, with Kaempferia galanga (50% w/w) as the main ingredient. The objective of this study was to investigate the anti-allergic activity of the crude extract from Prasaprohyai after accelerated stability test procedure. The method of extract used maceration in 95% ethanol and the crude extract was kept under accelerated condition at 40 ± 2 oC and 75 ± 5% relative humidity (RH) for six months. After six months of storage at 40 oC, the crude sample in various storage times (0, 15, 30, 45, 60, 90, 120, 150 and 180 days) were investigated for anti-allergic activity using IgE-sensitized RBL-2H3 cell lines. The results showed that the stability of crude ethanolic extract from Prasaprohyai under accelerated testing had no significant effect of anti-allergic activity when compared with day 0. The results showed that the ethanolic extract could be stored for two years at room temperature without loss of activity.

Keywords: accelerated stability, anti-allergy, prasaprohyai, RBL-2H3 cell lines

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Authors: Dwitya Elvira, Eryati Darwin

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Background: Graves’ disease (GD) is an autoimmune thyroid disease. Imbalance of Th1/Th2 cells and T-regulatory (Treg)/Th17 cells was thought to play pivotal role in the pathogenesis of GD. Treg FoxP3 produced TGF-β to maintain regulatory function, and Th17 cells produced IL-17 as cytokines that were thought in mediating several autoimmune diseases. The aim of this study is to assess the role of IL-17 and TGF-β in the pathogenesis of GD and to investigate its correlation with Thyroid Stimulating Hormone Receptor Antibody (TRAb) and Treg FoxP3 expression. Method: 30 GD patients and 27 age and sex-matched controls were enrolled in this study. Diagnosis of GD was based on clinical and biochemical of GD. Serum IL-17, TGF-β, TRAb, and FoxP3 were measured by enzyme-linked immunosorbent assay (ELISA). Data were analyzed by using SPSS 21.0 (SPSS Inc.). Spearman rank correlation test was used for assessment of correlation. The statistical significance was accepted as P<0.05. Result: There was no significant correlation between IL-17 and TGF-β serum with expression of FoxP3 level in GD, but there was significant correlation between TGF-β and TRAb serum level (P<0.05). Serum levels of IL-17 and TGF-β were found to be elevated in patient group compared to control, where mean values of IL-17 were 14.43±2.15 pg/mL and TGF-β were 10.44±3.19 pg/mL in patients group; and in control group, level of IL-17 were 7.1±1.45 pg/mL and TGF-β were 4.95±1.35 pg/mL. Conclusion: Serum Il-17 and TGF-β were elevated in GD patients that reflect the role of inflammatory and regulatory cytokines activation in pathogenesis of GD. There was significant correlation between TGF-β and TRAb, revealing that Treg cytokines may play a role in pathogenesis of GD.

Keywords: IL-17, TGF-B, FoxP3, TRAb, Graves’ disease

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Authors: Huong M. T. Nguyen, Hoa A. P. Nguyen, Mai P. T. Nguyen, Ngoc D. Ngo, Van T. Ta, Hai T. Le, Chi V. Phan

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Wilson’s disease (WD) is an autosomal recessive disorder of the copper metabolism, which is caused by a mutation in the copper-transporting P-type ATPase (ATP7B). The mechanism of this disease is the failure of hepatic excretion of copper to bile, and leads to copper deposits in the liver and other organs. The ATP7B gene is located on the long arm of chromosome 13 (13q14.3). This study aimed to investigate the gene mutation in the Vietnamese patients with WD, and make a presymptomatic diagnosis for their familial members. Forty-three WD patients and their 65 siblings were identified as having ATP7B gene mutations. Genomic DNA was extracted from peripheral blood samples; 21 exons and exon-intron boundaries of the ATP7B gene were analyzed by direct sequencing. We recognized four mutations ([R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G) in the sum of 20 detectable mutations, accounting for 87.2% of the total. Mutation S105* was determined to have a high rate (32.6%) in this study. The hotspot regions of ATP7B were found at exons 2, 16, and 8, and intron 14, in 39.6 %, 11.6 %, 9.3%, and 7 % of patients, respectively. Among nine homozygote/compound heterozygote siblings of the patients with WD, three individuals were determined as asymptomatic by screening mutations of the probands. They would begin treatment after diagnosis. In conclusion, 20 different mutations were detected in 43 WD patients. Of this number, four novel mutations were explored, including [R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G. The mutation S105* is the most prevalent and has been considered as a biomarker that can be used in a rapid detection assay for diagnosis of WD patients. Exons 2, 8, and 16, and intron 14 should be screened initially for WD patients in Vietnam. Based on risk profile for WD, genetic testing for presymptomatic patients is also useful in diagnosis and treatment.

Keywords: ATP7B gene, mutation detection, presymptomatic diagnosis, Vietnamese Wilson’s disease

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Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche

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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.

Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova

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Objectives. Gastrointestinal involvement is one of the most common manifestations of systemic sclerosis (SSc). The aim of our study was to assess the frequency of gastrointestinal manifestations in SSc patients (pts) with interstitial lung disease (ILD) and their changes to rituximab (RTX) therapy. Methods. There were 103 pts with SSc in this study. The mean follow-up period was 12.6±10.7 months. The mean age was 47±12.9 years, females - 87 pts (84%), and the diffuse cutaneous subset of the disease 55 pts (53%). The mean disease duration was 6.2±5.5 years. All pts had ILD and were positive for ANA. 67% of them were positive for anti-topoisomerase-1. All patients received prednisolone at a dose of 11.3±4.5 mg/day, and immunosuppressants at inclusion received 47% of them. Pts received RTX due to the ineffectiveness of previous therapy for ILD. The cumulative mean dose of RTX was 1.7±0.6 grams. 90% of pts received omeprazole at a dose of 20-40 mg/day. Results. At inclusion, dysphagia was observed in 76 pts (74%), early satiety or vomiting in 32 pts (31%), and diarrhea in 20 pts (19%). We didn't observe any changes in gastrointestinal manifestation during RTX therapy. There was a decrease in the number of pts with dysphagia from 76 (74%) to 66 (64%), but it was insignificant. The number of pts with early satiety or vomiting and diarrhea didn't change. Conclusion. In our study, gastrointestinal involvement was observed in most of the pts with SSc-ILD. We didn't find any significant changes in gastrointestinal manifestations during RTX therapy. RXT does not worsen gastrointestinal manifestations in SSc-ILD.

Keywords: systemic sclerosis, dysphagia, rituximab, gastrointestinal manifestations

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Authors: G. Tamilpavai, C. Vishnuppriya

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Studying DNA (deoxyribonucleic acid) sequence is useful in biological processes and it is applied in the fields such as diagnostic and forensic research. DNA is the hereditary information in human and almost all other organisms. It is passed to their generations. Earlier stage detection of defective DNA sequence may lead to many developments in the field of Bioinformatics. Nowadays various tedious techniques are used to identify defective DNA. The proposed work is to analyze and identify the cancer-causing DNA motif in a given sequence. Initially the human DNA sequence is separated as k-mers using k-mer separation rule. The separated k-mers are clustered using Self Organizing Map (SOM). Using Levenshtein distance measure, cancer associated DNA motif is identified from the k-mer clusters. Experimental results of this work indicate the presence or absence of cancer causing DNA motif. If the cancer associated DNA motif is found in DNA, it is declared as the cancer disease causing DNA sequence. Otherwise the input human DNA is declared as normal sequence. Finally, elapsed time is calculated for finding the presence of cancer causing DNA motif using clustering formation. It is compared with normal process of finding cancer causing DNA motif. Locating cancer associated motif is easier in cluster formation process than the other one. The proposed work will be an initiative aid for finding genetic disease related research.

Keywords: bioinformatics, cancer motif, DNA, k-mers, Levenshtein distance, SOM

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Authors: Fatimah Abd Elghani, Raymonde Szargel, Vered Shani, Hazem Safory, Haya Hamza, Mor Savyon, Ruth Rott, Rina Bandopadhyay, Simone Engelender

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Background: PINK1 is a mitochondrial kinase mutated in some familial cases of Parkinson’s disease. Down regulation of PINK1 results in abnormal mitochondrial morphology and altered membrane potential. Although PINK1 has a predicted mitochondrial import sequence, it’s cellular, and submitochondrial localization remains unclear, in part because it is rapidly degraded. In this work, we investigated the mechanisms involved in PINK1 degradation and how this may affect PINK1 stability and function, with implications for mitochondrial function in PD. In addition, pharmacological inhibition of proteasome activity was shown to lead to PINK1 accumulation, indicating that PINK1 degradation depends on the ubiquitin-proteasome system (UPS). Methods: Using co-immunoprecipitation assays, we identified E3 ubiquitin ligase SIAH1 as a PINK1-interacting protein in HEK293 cells as well as on rat brain tissues. In addition, we determined the effect of SIAH 1, SIAH2 and Parkin on PINK1 steady-state levels by Western blot analysis, and checked their possibility to ubiquitinate and mediate PINK1 degradation through the proteasome carried out in vivo ubiquitination experiments. Results: We have obtained results showing that SIAH-1 interacts with and ubiquitinates PINK1. The ubiquitination promoted by SIAH-1 leads to the proteasomal degradation of PINK1. We confirmed these findings by knocking down SIAH-1 and observing important accumulation of PINK1 in cells. Besides, we found that SIAH-1 decreases PINK1 steady-state levels but not the E3 ligase Parkin. We also investigated the interaction of SIAH-1 with PINK1 disease mutants and its ability to promote their ubiquitination and degradation. Although, no clear difference in the ability of SIAH-1 to promote the degradation of PINK1 disease mutants was observed. It is possible that dysfunction of proteasomal activity in the disease may lead to the accumulation and aggregation of ubiquitinated PINK1 in patients with PINK1 mutations, with possible implications to the pathogenesis of PD. Conclusions: Here, we demonstrated that SIAH-1 ubiquitinates and promotes the degradation of PINK1. In addition, SIAH-1 represents now a target that may help the improvement of mitophagy in PD. Further investigations needed to understand how mitophagy is regulated by PINK1-SIAH-1 axis to provide targets for future therapeutics.

Keywords: PD, Parkinson's disease, PINK1, PTEN-induced kinase1, SIAH, seven in absentia homolog, SN, substantia nigra

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Authors: Mochammad Indra Permana, Andhiani Sharfina Arnellya, Dika Pramita Destiani, Budhi Prihartanto

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Cardiovascular disease is the cause of the highest mortality rates in the world. The number of cardiovascular disease patients is increasing every year. Data obtained from World Health Organization (WHO) that 17,5 million people died from this disease. The condition of cardiovascular diseases such as atrial fibrillation, myocardial infarction, venous thromboembolism, and several other conditions need anticoagulant therapy. Results of the anticoagulant therapy are measured not only by the effectiveness of International Normalized Ratio (INR) value but also by the quality of life of the patients. The purpose of this study was to determine the quality of life of patients on oral anticoagulant therapy in outpatient cardiac department Dr. Hasan Sadikin central general hospital, Bandung, Indonesia. This is a cross-sectional study with collecting data from the quality of life questionnaire and medical record of the patients. The results of this study showed that 28 patients (46,7%) had a good quality of life, 30 patients (50%) had a moderate quality of life, and 2 patients (3,3%) had a poor quality of life with no significant differences in quality of life based on age, gender, diagnosis, and duration of drug use.

Keywords: anticoagulant, cardiovascular diseases, INR, quality of life

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Authors: Mohammed E. Mansour, Tamador M. A. Elhassan, Nahid A. Ibrahim, Awatif A. Ahmed, Manal A. Abdalla

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Rift valley fever (RVF) is mosquito-borne disease. RVF is transboundary zoonotic disease. It has socioeconomic and public health importance. This paper describes qualitative risk of the RVF vaccine production. RVF is endemic in the Sudan. It has been reported in Sudan due to abundance of Ades Eqytie. Thus, there is huge effort to control it. Vaccination practices had significant role to control and manage RVF. The risk assessment explains the likelihood of a risk as likely. Thus, insecticides and repellents synergize the effort of the vaccination.

Keywords: qualitative analysis, risk assessment, rift valley fever vaccine, quality control

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Authors: Harshadkumar Rajgor, Jeff Butterworth

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Background: Barretts oesophagus increases the risk of developing oesophageal adenocarcinoma. Over the last 40 years, there has been a 6 fold increase in the incidence of oesophageal adenocarcinoma in the western world and the incidence rates are increasing at a greater rate than cancers of the colon, breast and lung. Endoscopic mucosal resection (EMR) is a relatively new technique being used by 2 centres in the greater midlands cancer network. EMR can be used for curative or staging purposes, for high-grade dysplasia’s and T1 tumours of the oesophagus. EMR is also suitable for those who are deemed high risk for oesophagectomy. EMR has a recurrence rate of 21% according to the Wiesbaden data. Method: A retrospective study of prospectively collected data was carried out involving 24 patients who had EMR for curative or staging purposes. Complications of residual or recurrent disease following EMR that required further treatment were investigated. Results: In 54% of cases residual or recurrent disease was suspected. 96% of patients were given clear and concise information regarding their diagnosis of high-grade dysplasia or T1 tumours. All 24 patients consulted the same specialist healthcare team. Conclusion: EMR is a safe and effective treatment for patients who have high-grade dysplasia and T1NO tumours. In 54% of cases residual or recurrent disease was suspected. Initially, only single resections were undertaken. Multiple resections are now being carried out to reduce the risk of recurrence. Complications from EMR remain low in this series and consisted of a single episode of post procedural bleeding.

Keywords: endoscopic mucosal resection, oesophageal dysplasia, T1 tumours, cancer network

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Authors: Ying Zhu, Ning Wu, Hai-Dong Huang, Yu-Chao Dong, Qin-Ying Sun, Wei Zhang, Qin Wang, Qiang Li

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Background and study aims: Tracheobronchopathia osteochondroplastica (TO) is an uncommon disease of the tracheobronchial system that leads to narrowing of the airway lumen from cartilaginous and/or osseous submucosal nodules. The aim of this study is to perform a detailed review of this rare disease in a large cohort of patients with TO proven by fiberoptic bronchoscopy from China. Patients and Methods: Retrospective chart review was performed on 41,600 patients who underwent bronchoscopy in the Department of Respiratory Medicine of Changhai Hospital between January 2005 and December 2012. Cases of TO were identified based on characteristic features during bronchoscopic examination. Results: 22 cases of bronchoscopic TO were identified. Among whom one-half were male and the mean age was 47.45 ±10.91 years old. The most frequent symptoms at presentation were chronic cough (n=14) and increased sputum production (n=10). Radiographic abnormalities were observed in 3/18 patients and findings on computed tomography consistent with TO such as beaded intraluminal calcifications and/or increased luminal thickenings were observed in 18/22 patients. Patients were classified into the following categories based on the severity of bronchoscopic findings: Stage I (n=2), Stage II (n=6) and Stage III(n=14). The result that bronchoscopic improvement was observed in 2 patients administered with inhaled corticosteroids suggested that resolution of this disease is possible. Conclusions: TO is a benign disease with slow progression, which could be roughly divided into 3 stages on the basis of the characteristic endoscopic features and histopathologic findings. Chronic inflammation was thought to be more important than the other existing plausible hypotheses in the course of TO. Inhaled corticosteroids might have some impact on patients at Stage I/II.

Keywords: airway obstruction, bronchoscopy, etiology, Tracheobronchopathia osteochondroplastica (TO), treatment

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Authors: Zi-Han Li, Zi-Jun Sun, Dong-Yuan Chang, Li Zhu, Min Chen, Ming-Hui Zhao

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Aims: A genome-wide association study (GWAS) reported that patients with the rs55703767 minor allele in collagen type IV α3 chain encoding gene COL4A3 showed protection against diabetic kidney disease (DKD) in type 1 diabetes mellitus (T1DM). However, the role of rs55703767 in type 2 DKD has not been elucidated. The aim of the current study was to investigate the association between COL4A3 variant rs55703767 and DKD risk in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: This nested case-control study was performed on 1311 patients who had T2DM for at least 10 years, including 580 with DKD and 731 without DKD. We detected the genotypes of all patients by TaqMan SNP Genotyping Assay and analyzed the association between COL4A3 variant rs55703767 and DKD risk. Results: Genetic analysis revealed that there was no significant difference between T2DM patients with DKD and those without DKD regarding allele or genotype frequencies of rs55703767, and the effect of this variant was not hyperglycemia specific. Conclusion: Our findings suggested that there was no detectable association between the COL4A3 variant rs55703767 and the susceptibility to DKD in the Chinese T2DM population.

Keywords: collagen type IV α3 chain, gene polymorphism, type 2 diabetes, diabetic kidney disease

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Authors: Xuzhen Yang, Yan Shan, Yabo Ding, Keke DIao, Yanjun Zhang, Yijia Huang

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Purpose: Our aim is to understand the unique experiences of patients with peritoneal dialysis and how they deal with issues brought on by disease and dialysis. Patients and Methods: Semi-structured interview was designed to collect information, and inpatients with peritoneal dialysis in a university-based tertiary hospital in the central province of China were purposively chosen as interviewees. The content analysis method was used to analyze the data. Results: Nine patients participated in the study, and three themes and eight subthemes were generated. Conclusion: Patients using peritoneal dialysis encounter numerous challenges and problems in the process of disease and dialysis, and they took attempt to cope with them well to adapt to living with peritoneal dialysis.

Keywords: peritoneal dialysis, experience, patient, coping strategy

Procedia PDF Downloads 99

Authors: Korpapa Srisamai, Pawee Siriruk

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The purpose of this study is to forecast product demands and develop appropriate and adequate procurement plans to meet customer needs and reduce costs. When the product exceeds customer demands or does not move, it requires the company to support insufficient storage spaces. Moreover, some items, when stored for a long period of time, cause deterioration to dead stock. A case study of the wholesale company of electronic equipment and components, which has uncertain customer demands, is considered. The actual purchasing orders of customers are not equal to the forecast provided by the customers. In some cases, customers have higher product demands, resulting in the product being insufficient to meet the customer's needs. However, some customers have lower demands for products than estimates, causing insufficient storage spaces and dead stock. This study aims to reduce the loss of sales opportunities and the number of remaining goods in the warehouse, citing 30 product samples of the company's most popular products. The data were collected during the duration of the study from January to October 2022. The methods used to forecast are simple moving averages, weighted moving average, and exponential smoothing methods. The economic ordering quantity and reorder point are used to calculate to meet customer needs and track results. The research results are very beneficial to the company. The company can reduce the loss of sales opportunities by 20% so that the company has enough products to meet customer needs and can reduce unused products by up to 10% dead stock. This enables the company to order products more accurately, increasing profits and storage space.

Keywords: demand forecast, reorder point, lost sale, dead stock

Procedia PDF Downloads 121

Authors: Kamil Ganaev, Elina Vlasova, Andrei Shiryaev, Renat Akchurin

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De novo atrial fibrillation (AF) after coronary artery bypass grafting (CABG) is a common complication. To date, there are no data on the possible effect of diffuse lesions of coronary arteries on the incidence of postoperative AF complications. Methods. Patients operated on-pump under hypothermic conditions during the calendar year (2020) were studied. Inclusion criteria - isolated CABG and achievement of complete myocardial revascularization. Patients with a history of AF moderate and severe valve dysfunction, hormonal thyroid pathology, initial CHF(Congestive heart failure), as well as patients with developed perioperative complications (IM, acute heart failure, massive blood loss) and deceased were excluded. Thus 227 patients were included; mean age 65±9 years; 69% were men. 89% of patients had a 3-vessel lesion of the coronary artery; the remainder had a 2-vessel lesion. Mean LV size: 3.9±0.3 cm, indexed LV volume: 29.4±5.3 mL/m2. Two groups were considered: D (n=98), patients with diffuse coronary heart disease, and L (n=129), patients with local coronary heart disease. Clinical and demographic characteristics in the groups were comparable. Rhythm assessment: continuous bedside ECG monitoring up to 5 days; ECG CT at 5-7 days after CABG; daily routine ECG registration. Follow-up period - postoperative hospital period. Results. The Median follow-up period was 9 (7;11) days. POFP (Postoperative atrial fibrillation) was detected in 61/227 (27%) patients: 34/98 (35%) in group D versus 27/129 (21%) in group L; p<0.05. Moreover, the values of revascularization index in groups D and L (3.9±0.7 and 3.8±0.5, respectively) were equal, and the mean time Cardiopulmonary bypass (CPB) (107±27 and 80±13min), as well as the mean ischemic time (67±17 and 55±11min) were significantly longer in group D (p<0.05). However, a separate analysis of these parameters in patients with and without developed AF did not reveal any significant differences in group D (CPB time 99±21.2 min, ischemic time 63±12.2 min), or in group L (CPB time 88±13.1 min, ischemic time 58.7±13.2 min). Conclusion. With the diffuse nature of coronary lesions, the incidence of AF in the hospital period after isolated CABG definitely increases. To better understand the role of severe coronary atherosclerosis in the development of POAF, it is necessary to distinguish the influence of organic features of atrial and ventricular myocardium (as a consequence of chronic coronary disease) from the features of surgical correction in diffuse coronary lesions.

Keywords: atrial fibrillation, diffuse coronary artery disease, coronary artery bypass grafting, local coronary artery disease

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Authors: Paul Essel, Eric T. Glover, Gustav Gbeddy, Yaw Adjei-Kyereme, Abdallah M. A. Dawood, Evans M. Ameho, Emmanuel A. Aberikae

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Radioactive materials mainly in the form of Sealed Radioactive Sources are being used in various sectors (medicine, agriculture, industry, research, and teaching) for the socio-economic development of Ghana. The use of these beneficial radioactive materials has resulted in an inventory of Disused Sealed Radioactive Sources (DSRS) in storage. Most of the DSRS are legacy/historic sources which cannot be returned to their manufacturer or country of origin. Though small in volume, DSRS can be intensively radioactive and create a significant safety and security liability. They need to be managed in a safe and secure manner in accordance with the fundamental safety objective. The Radioactive Waste Management Center (RWMC) of the Ghana Atomic Energy Commission (GAEC) is currently storing a significant volume of DSRS. The initial activities of the DSRS range from 7.4E+5 Bq to 6.85E+14 Bq. If not managed properly, such DSRS can represent a potential hazard to human health and the environment. Storage is an important interim step, especially for DSRS containing very short-lived radionuclides, which can decay to exemption levels within a few years. Long-term storage, however, is considered an unsustainable option for DSRS with long half-lives hence the need for a disposal facility. The GAEC intends to use the International Atomic Energy Agency’s (IAEA’s) Borehole Disposal System (BDS) to provide a safe, secure, and cost-effective disposal option to dispose of its DSRS in storage. The proposed site for implementation of the BDS is on the GAEC premises at Kwabenya. The site has been characterized to gain a general understanding in terms of its regional setting, its past evolution and likely future natural evolution over the assessment time frame. Due to the long half-lives of some of the radionuclides to be disposed of (Ra-226 with half-life of 1600 years), the engineered barriers of the system must be robust to contain these radionuclides for this long period before they decay to harmless levels. There is the need to assess the safety related functions of the engineered barriers of this disposal system.

Keywords: radionuclides, disposal, radioactive waste, engineered barrier

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Authors: Supriyono, Sumardiyono, Rendy J. Pramono

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Biodiesel is one of the alternative fuels promising for substituting petrodiesel as energy source which has an advantage as it is sustainable and eco-friendly. Due to the raw material that tends to decompose during storage, biodiesel also has the same characteristic that tends to decompose during storage. Biodiesel decomposition will form higher acid value as the result of oxidation to double bond on a fatty acid compound on biodiesel. Thus, free fatty acid value could be used to evaluate degradation of biodiesel due to the oxidation process. High free fatty acid on biodiesel could impact on the engine performance. Decomposition of biodiesel due to oxidation reaction could prevent by introducing a small amount of antioxidant. The origin of raw materials and the process for producing biodiesel will determine the effectiveness of antioxidant. Biodiesel made from high free fatty acid (FFA) crude palm oil (CPO) by using two steps esterification is vulnerable to oxidation process which is resulted in increasing on the FFA value. Tocopherol also known as vitamin E is one of the antioxidant that could improve the stability of biodiesel due to decomposition by the oxidation process. Tocopherol 0.5% concentration on palm oil biodiesel could reduce 13% of increasing FFA under temperature 80 °C and exposing time 180 minute.

Keywords: antioxidant, palm oil biodiesel, decomposition, oxidation, tocopherol

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Authors: Mathieu Imbert, Sebastien Comas-Cardona, Emmanuelle Abisset-Chavanne, David Prono

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Short cycle time Resin Transfer Molding (RTM) applications appear to be of great interest for the mass production of automotive or aeronautical lightweight structural parts. During the RTM process, the two components of a resin are mixed on-line and injected into the cavity of a mold where a fibrous preform has been placed. Injection and polymerization occur simultaneously in the preform inducing evolutions of temperature, degree of cure and viscosity that furthermore affect flow and curing. In order to adjust the processing conditions to reduce the cycle time, it is, therefore, essential to understand and quantify the physical mechanisms occurring in the part during injection. In a previous study, a dual-scale simulation tool has been developed to help determining the optimum injection parameters. This tool allows tracking finely the repartition of the resin and the evolution of its properties during reactive injections with on-line mixing. Tows and channels of the fibrous material are considered separately to deal with the consequences of the dual-scale morphology of the continuous fiber textiles. The simulation tool reproduces the unsaturated area at the flow front, generated by the tow/channel difference of permeability. Resin “storage” in the tows after saturation is also taken into account as it may significantly affect the repartition and evolution of the temperature, degree of cure and viscosity in the part during reactive injections. The aim of the current study is, thanks to experiments, to understand and quantify the “storage” evolution in the tows to adjust and validate the numerical tool. The presented study is based on four experimental repeats conducted on three different types of textiles: a unidirectional Non Crimp Fabric (NCF), a triaxial NCF and a satin weave. Model fluids, dyes and image analysis, are used to study quantitatively, the resin flow in the saturated area of the samples. Also, textiles characteristics affecting the resin “storage” evolution in the tows are analyzed. Finally, fully coupled on-line mixing reactive injections are conducted to validate the numerical model.

Keywords: experimental, on-line mixing, high-speed RTM process, dual-scale flow

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Authors: Jung-Hwan Oh, Rajesh Kumar, Il-Kwon Oh

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Porous graphene has extensive potential applications in variety of fields such as hydrogen storage, CO oxidation, gas separation, supercapacitors, fuel cells, nanoelectronics, oil adsorption, and so on. However, the generation of some carbon atoms vacancies for precise small holes have been not extensively studied to prevent the agglomerates of graphene sheets and to obtain porous graphene with high surface area. Recently, many research efforts have been presented to develop physical and chemical synthetic approaches for porous graphene. But physical method has very high cost of manufacture and chemical method consumes so many hours for porous graphene. Herein, we propose a porous graphene contained holes with atomic scale precision by embedding metal nano-particles through microwave irradiation for hydrogen storage and CO oxidation multi- functionalities. This proposed synthetic method is appropriate for fast and convenient production of three dimensional nanostructures, which have nanoholes on the graphene surface in consequence of microwave irradiation. The metal nanoparticles are dispersed quickly on the graphene surface and generated uniform nanoholes on the graphene nanosheets. The morphological and structural characterization of the porous graphene were examined by scanning electron microscopy (SEM), transmission scanning electron microscopy (TEM) and RAMAN spectroscopy, respectively. The metal nanoparticle-embedded porous graphene exhibits a microporous volume of 2.586cm3g-1 with an average pore radius of 0.75 nm. HR-TEM analysis was carried out to further characterize the microstructures. By investigating the RAMAN spectra, we can understand the structural changes of graphene. The results of this work demonstrate a possibility to produce a new class of porous graphene. Furthermore, the newly acquired knowledge for the diffusion into graphene can provide useful guidance for the development of the growth of nanostructure.

Keywords: CO oxidation, hydrogen storage, nanocomposites, porous graphene

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Authors: D. M. Tshwane, R. R. Maphanga, P. E. Ngoepe

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Nanostructured materials are attractive candidates for efficient electrochemical energy storage devices because of their unique physicochemical properties. Nanotubes have drawn a continuous attention because of their unique electrical, optical and magnetic properties contrast to that of bulk system. They have potential application in the field of optical, electronics and energy storage device. Introducing nanotubes structures as electrode materials; represents one of the most attractive strategies that could dramatically enhance the battery performance. Spinel LiMn2O4 is the most promising cathode material for Li-ion batteries. In this work, computer simulation methods are used to generate and investigate properties of spinel LiMn2O4 nanotubes. Molecular dynamic simulation is used to probe the local structure of LiMn2O4 nanotubes and the effect of temperature on these systems. It is found that diameter, Miller indices and size have a direct control on nanotubes morphology. Furthermore, it is noted that stability depends on surface and wrapping of the nanotube. The nanotube structures are described using the radial distribution function and XRD patterns. There is a correlation between calculated XRD and experimentally reported results.

Keywords: LiMn2O4, li-ion batteries, nanotubes, nanostructures

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Authors: Luiz Daniel Garay Trindade, Antonio De Freitas Valle Neto, Fabio Paulo Basso, Elder De Macedo Rodrigues, Maicon Bernardino, Daniel Welfer, Daniel Muller

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Agriculture plays an important role in society since it is one of the main sources of food in the world. To help the production and yield of crops, precision agriculture makes use of technologies aiming at improving productivity and quality of agricultural commodities. One of the problems hampering quality of agricultural production is the disease affecting crops. Failure in detecting diseases in a short period of time can result in small or big damages to production, causing financial losses to farmers. In order to provide a map of the contributions destined to the early detection of plant diseases and a comparison of the accuracy of the selected studies, a systematic literature review of the literature was performed, showing techniques for digital image processing and neural networks. We found 35 interesting tool support alternatives to detect disease in 19 plants. Our comparison of these studies resulted in an overall average accuracy of 87.45%, with two studies very closer to obtain 100%.

Keywords: pattern recognition, image processing, deep learning, precision agriculture, smart farming, agricultural automation

Procedia PDF Downloads 379