Search results for: neglected tropical disease

Authors: Attila Simon

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Since the publication of Franz Cumont, there have been countless works on the mysteries of Mithras and the iconography of Mithraic, but there are elements that have received less attention in research. Most of the works on the subject deal with the bull-killing-motif, whose astronomical significance has been well proven by several eminent scholars. Among the iconographic elements that survive in the reliefs and frescoes of Mithras, there are several that have not yet been clearly interpreted. These include the depiction of a bull in the boat, which occurred mainly in the Danubian provinces. Using CIMRM, one collected the cases that contain the motif under study, created a database of them grouped by location, and then used a comparative method to compare the representations adjacent to the motif. The aim of this research is to find an explanation for this neglected motif in the iconography of Mithras and to try to map its origins. The interpretation may be given to a mithraic representation for which to the author’s best knowledge no explanation has been given so far, and the question may be reopened for discussion.

Keywords: roman history, religion, Mithras, iconography

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Authors: Mojgan Rabiey, Shyamali Roy, Billy Quilty, Ryan Creeth, George Sundin, Robert W. Jackson

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Bacterial canker is a major disease of Prunus species such as cherry (Prunus avium). It is caused by Pseudomonas syringae species including P. syringae pv. syringae (Pss) and P. syringae pv. morsprunorum race 1 (Psm1) and race 2 (Psm2). Concerns over the environmental impact of, and developing resistance to, copper controls call for alternative approaches to disease management. One method of control could be achieved using naturally occurring bacteriophage (phage) infective to the bacterial pathogens. Phages were isolated from soil, leaf, and bark of cherry trees in five locations in the South East of England. The phages were assessed for their host range against strains of Pss, Psm1, and Psm2. The phages exhibited a differential ability to infect and lyse different Pss and Psm isolates as well as some other P. syringae pathovars. However, the phages were unable to infect beneficial bacteria such as Pseudomonas fluorescens. A subset of 18 of these phages were further characterised genetically (Random Amplification of Polymorphic DNA-PCR fingerprinting and sequencing) and using electron microscopy. The phages are tentatively identified as belonging to the order Caudovirales and the families Myoviridae, Podoviridae, and Siphoviridae, with genetic material being dsDNA. Future research will fully sequence the phage genomes. The efficacy of the phage, both individually and in cocktails, to reduce disease progression in vivo will be investigated to understand the potential for practical use of these phages as biocontrol agents.

Keywords: bacteriophage, pseudomonas, bacterial cancker, biological control

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Authors: Ashima Sharma, Tapan K. Chaudhuri

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Human Serum Albumin (HSA) is one of the most demanded therapeutic protein with immense biotechnological applications. The current source of HSA is human blood plasma. Blood is a limited and an unsafe source as it possesses the risk of contamination by various blood derived pathogens. This issue led to exploitation of various hosts with the aim to obtain an alternative source for the production of the rHSA. But, till now no host has been proven to be effective commercially for rHSA production because of their respective limitations. Thus, there exists an indispensable need to promote non-animal derived rHSA production. Of all the host systems, Escherichia coli is one of the most convenient hosts which has contributed in the production of more than 30% of the FDA approved recombinant pharmaceuticals. E. coli grows rapidly and its culture reaches high cell density using inexpensive and simple substrates. The fermentation batch turnaround number for E. coli culture is 300 per year, which is far greater than any of the host systems available. Therefore, E. coli derived recombinant products have more economical potential as fermentation processes are cheaper compared to the other expression hosts available. Despite of all the mentioned advantages, E. coli had not been successfully adopted as a host for rHSA production. The major bottleneck in exploiting E. coli as a host for rHSA production was aggregation i.e. majority of the expressed recombinant protein was forming inclusion bodies (more than 90% of the total expressed rHSA) in the E. coli cytosol. Recovery of functional rHSA form inclusion body is not preferred because it is tedious, time consuming, laborious and expensive. Because of this limitation, E. coli host system was neglected for rHSA production for last few decades. Considering the advantages of E. coli as a host, the present work has targeted E. coli as an alternate host for rHSA production through resolving the major issue of inclusion body formation associated with it. In the present study, we have developed a novel and innovative method for enhanced soluble and functional production of rHSA in E.coli (~60% of the total expressed rHSA in the soluble fraction) through modulation of the cellular growth, folding and environmental parameters, thereby leading to significantly improved and enhanced -expression levels as well as the functional and soluble proportion of the total expressed rHSA in the cytosolic fraction of the host. Therefore, in the present case we have filled in the gap in the literature, by exploiting the most well studied host system Escherichia coli which is of low cost, fast growing, scalable and ‘yet neglected’, for the enhancement of functional production of HSA- one of the most crucial biomolecule for clinical and biotechnological applications.

Keywords: enhanced functional production of rHSA in E. coli, recombinant human serum albumin, recombinant protein expression, recombinant protein processing

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Authors: Nadia Akbarpour

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Pancreatic ductal adenocarcinoma is a forceful and obliterating illness, which is portrayed by intrusiveness, fast movement, and significant protection from treatment. Advances in neurotic arrangement and malignant growth hereditary qualities have worked on our illustrative comprehension of this infection; be that as it may, significant parts of pancreatic disease science remain ineffectively comprehended. A superior comprehension of pancreatic disease science should lead the way to more viable medicines. In the course of the most recent couple of years, there have been significant advances in the sub-atomic and organic comprehension of pancreatic malignancy. This included comprehension of the genomic intricacy of the illness, the job of pancreatic malignant growth undifferentiated organisms, the importance of the growth microenvironment, and the one-of-a-kind metabolic transformation of pancreas disease cells to acquire supplements under hypoxic climate. Endeavors have been made towards the advancement of the practical answer for its treatment with compelled achievement due to its complicated science. It is grounded that pancreatic malignancy undifferentiated cells (CSCs), yet present in a little count, contribute extraordinarily to PC inception, movement, and metastasis. Standard chemo and radiotherapeutic choices, notwithstanding, grow general endurance, the connected aftereffects are a huge concern. In the midst of the latest decade, our understanding with regards to atomic and cell pathways engaged with PC and the job of CSCs in its movement has expanded massively. By and by, the center is to target CSCs. The natural items have acquired a lot of thought as of late as they, generally, sharpen CSCs to chemotherapy and target atomic flagging engaged with different cancers, including PC. Some arranged investigations have demonstrated promising outcomes recommending that assessments in this course bring a ton to the table for the treatment of PC. Albeit preclinical investigations uncovered the significance of natural items in lessening pancreatic carcinoma, restricted examinations have been led to assess their part in centers. The current survey gives another knowledge to late advances in pancreatic malignancy science, treatment, and the current status of natural items in its expectation.

Keywords: pancreatic, genomic, organic, cancer

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Authors: Ahmed Zaghawa

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Rift Valley Fever is an economically specific disease of the health and arboviral disease that affects many types of animals, causing significant economic losses in livestock, and it is transmitted to humans and has public health issues. The vaccine program is the backbone for the control of this disease. The goal of this study was to apply a new approach to evaluate the inactivated RVF vaccine developed in Egypt. In this study, the RVF vaccine was evaluated in young puppies and compared with sheep; the findings showed that young puppies were susceptible to infection with the inhibitory RVF virus and had a strong response of antibodies with two doses of the RVF vaccine within the two-week interval. The neutralization indices began to appear to the protective level on the 7th day at 1.35 and steadily elevated at 14,21 and 28 days to 1.35, 1.43, and 1.20, respectively, in comparison to the control group. While in sheep, the neutralization indices began to appear to the protective level on the 7th day at 1.10 and remain strongly at high titer at 14, 21, and 28 days with NI values 1.20, 1.50, and 1.50, respectively. The new approach for comparing the immune response in puppies and sheep via SNT indicated the high response in both species was evident as well as the neutralization indices values in young puppies at different periods after RVF vaccination reported the value of 1.08±0.03, 1.23±0.04, 1.30±0.03, and 1.45±0.02 after 7, 14, 21, and 28 days post-vaccination respectively. On the other side, a nearly similar immune response was noticed in sheep with NI values of 1.15±0.02, 1.27±0.02, 1.42±0.05, and 1.55±0.03 at 7, 14, 21, and 28 days post-vaccination, respectively. In conclusion, young puppies are similar to sheep in developing antibodies after vaccination with the RVF vaccine and can replace sheep for evaluating the efficacy of the RVF vaccine. Further studies are mandatory to assess more recent methods for evaluating inhibition of the RVF vaccine.

Keywords: immune response, puppies, RVF, sheep, vaccine

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Authors: Hailu Getnet

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This study focus on reverse innovation on performance outcomes across developed and subsistence markets context. The subsistence market consists two third of the world population and the largest international market. To date, it has been neglected because of its issues of perceived challenges and seeming unattractiveness compared to the established markets in the west. However, subsistence markets are becoming source of reverse innovation; an innovation that is likely to be adopted first in developing world and successfully traded globally. In response, there is a growing interest on reverse innovation to power the future. Based on the theories of innovation and growing subsistence market literatures, the study propose drivers and outcomes of reverse innovation, a potential similarities and difference in benefiting and challenging firms and consumers in subsistence and developed markets.

Keywords: reverse innovation, subsistence market, developing world, developed market

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Authors: Anthony Barker, Roland Jiang

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Dupuytren’s contractures are a debilitating condition affecting the palmar fascia of the hand reducing its function. This case series looks at the minimally-invasive technique of Xiaflex injections and the outcome in a public health setting. 15 patients undertook collagenase injection (Xiaflex, C. histolyticum) injection over the period from September 2015 to May 2017 at Fairfield Hospital, NSW. Their reported outcome post injection and in follow-up was recorded as well as their satisfaction and likelihood to request the procedure in the future. Other treatment modalities include percutaneous needle aponeurotomy, limited palmar fasciotomy, and palmar fasciectomy. A literature review of cost-effectiveness was performed to compare Xiaflex suitability for waitlist reduction in a public setting given average waiting times in the public setting extend past 365 days.

Keywords: Dupuytrens Disease, xiaflex, collagenase, plastic surgery

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Authors: Mario Isaza-Ruget, Claudia C. Colmenares-Mejia, Nancy Yomayusa, Camilo A. González, Andres Cely, Jossie Murcia

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Quantification of risks associated with complications development from chronic kidney disease (CKD) through accurate survival models can help with patient management. A retrospective cohort that included patients diagnosed with CKD from a primary care program and followed up between 2013 and 2018 was carried out. Time-dependent and static covariates associated with demographic, clinical, and laboratory factors were included. Deep Learning (DL) survival analyzes were developed for three CKD outcomes: CKD stage progression, >25% decrease in Estimated Glomerular Filtration Rate (eGFR), and Renal Replacement Therapy (RRT). Models were evaluated and compared with Random Survival Forest (RSF) based on concordance index (C-index) metric. 2.143 patients were included. Two models were developed for each outcome, Deep Neural Network (DNN) model reported C-index=0.9867 for CKD stage progression; C-index=0.9905 for reduction in eGFR; C-index=0.9867 for RRT. Regarding the RSF model, C-index=0.6650 was reached for CKD stage progression; decreased eGFR C-index=0.6759; RRT C-index=0.8926. DNN models applied in survival analysis context with considerations of longitudinal covariates at the start of follow-up can predict renal stage progression, a significant decrease in eGFR and RRT. The success of these survival models lies in the appropriate definition of survival times and the analysis of covariates, especially those that vary over time.

Keywords: artificial intelligence, chronic kidney disease, deep neural networks, survival analysis

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Authors: Muhammad Yousaf Ali, Shahid Mansoor, Javeria Qazi, Imran Amin, Musarrat Shaheen

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Cotton leaf curl disease (CLCuD) is the major threat to the cotton crop and is transmitted by whitefly (Bemisia tabaci). Since multiple begomoviruses and associated satellites are involved in CLCuD, approaches based on the concept of broad-spectrum resistance are essential for effective disease control. Gro-El and G5 are two proteins from whitefly endosymbiont and M13 bacteriophage origin, respectively. Gro-El encapsulates the virus particle when it enters the whitefly and protects the virus from the immune system of the whitefly as well as prevents viral expression in it. This characteristic of Gro-El can be exploited to get resistance against viruses if expressed in plants. G5 is a single-stranded DNA binding protein, expression of which in transgenic plants will stop viral expression on its binding with ssDNA. The use of tissue-specific promoters is more efficient than constitutive promoters. Transgenics of Nicotiana benthamiana for Gro-El under constitutive promoter and Gro-El under phloem specific promoter were made. In comparison to non-transgenic plants, transgenic plants with Gro-El under NSP promoter showed promising results when challenged against cotton leaf curl Multan virus (CLCuMuV) along with cotton leaf curl Multan beta satellite (CLCuMB), cotton leaf curl Khokhran virus (CLCuKoV) along with cotton leaf curl Multan beta satellite (CLCuMB) and Pedilenthus leaf curl virus (PedLCV) along with Tobacco leaf curl beta satellite (TbLCB).

Keywords: cotton leaf curl disease, whitefly, endosymbionts, transgenic, resistance

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Authors: Arrate Barrenechea Garro

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Background: Bilingualism has been shown to enhance cognitive reserve and potentially delay the onset of dementia symptoms. This study investigates the impact of bilingualism on cognitive reserve and the age of diagnosis in Parkinson's Disease (PD). Methodology: The study involves 16 non-demented monolingual PD patients and 12 non-demented bilingual PD patients, matched for age, sex, and years of education. All participants are native Spanish speakers, with Spanish as their first language (L1). Cognitive performance is assessed through a neuropsychological examination covering all cognitive domains. Cognitive reserve is measured using the Cognitive Reserve Index Questionnaire (CRIq), while language proficiency is evaluated using the Bilingual Language Profile (BLP). The age at diagnosis is recorded for both monolingual and bilingual patients. Results: Bilingual PD patients demonstrate higher scores on the CRIq compared to monolingual PD patients, with significant differences between the groups. Furthermore, there is a positive correlation between cognitive reserve (CRIq) and the utilization of the second language (L2) as indicated by the BLP. Bilingual PD patients are diagnosed, on average, three years later than monolingual PD patients. Conclusion: Bilingual PD patients exhibit higher levels of cognitive reserve compared to monolingual PD patients, as indicated by the CRIq scores. The utilization of the second language (L2) is positively correlated with cognitive reserve. Bilingual PD patients are diagnosed with PD, on average, three years later than monolingual PD patients. These findings suggest that bilingualism may contribute to cognitive reserve and potentially delay the onset of clinical symptoms associated with PD. This study adds to the existing literature supporting the relationship between bilingualism and cognitive reserve. Further research in this area could provide valuable insights into the potential protective effects of bilingualism in neurodegenerative disorders.

Keywords: bilingualis, cogntiive reserve, diagnosis, parkinson's disease

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Authors: Simone Rondelli, Damiano Rondelli, Bishesh Poudyal, Juan Jose Cabrera-Lazarini

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One of the main obstacles for Social Entrepreneurship is to find a business model that is financially sustainable. In other words, the captured value generates enough cash flow to ensure business continuity and reinvestment for growth. Providing Health Services in poor countries for the uninsured population affected by a high-cost chronical disease is not the exception for this challenge. As a prime example, cancer has become a high impact on a global disease not only because of the high morbidity but also of the financial impact on both the patient family and health services in underdeveloped countries. Therefore, it is relevant to find a Social Entrepreneurship Model that provides affordable treatment for this disease while maintaining healthy finances not only for the patient but also for the organization providing the treatment. Using the methodology of Constructive Research, this paper applied a Positive Theory and four business models of Social Entrepreneurship to a case of a Private Foundation model whose mission is to address the challenge previously described. It was found that the Foundation analyzed, in this case, is organized as an Embedded Business Model and complies with the four propositions of the Positive Theory considered. It is recommended for this Private Foundation to explore implementing the Integrated Business Model to ensure more robust sustainability in the long term. It evolves as a scalable model that can attract investors interested in contributing to expanding this initiative globally.

Keywords: affordable treatment, global healthcare, social entrepreneurship theory, sustainable business model

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Authors: Justin Fu, Thomas Mazzuchi, Shahram Sarkani

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A key factor in technological immaturity in defense weapons acquisition is lack of understanding critical integrations at the subsystem and component level. To address this shortfall, recent research in integration readiness level (IRL) combines with technology readiness level (TRL) to form a system readiness level (SRL). SRL can be enriched with more robust quantitative methods to provide the program manager a useful tool prior to committing to major weapons acquisition programs. This research harnesses previous mathematical models based on graph theory, Petri nets, and tropical algebra and proposes a modification of the desirable SRL mathematical properties such that a tightly integrated (multitude of interfaces) subsystem can display a lower SRL than an inherently less coupled subsystem. The synthesis of these methods informs an improved decision tool for the program manager to commit to expensive technology development. This research ties the separately developed manufacturing readiness level (MRL) into the network representation of the system and addresses shortfalls in previous frameworks, including the lack of integration weighting and the over-importance of a single extremely immature component. Tropical algebra (based on the minimum of a set of TRLs or IRLs) allows one low IRL or TRL value to diminish the SRL of the entire system, which may not be reflective of actuality if that component is not critical or tightly coupled. Integration connections can be weighted according to importance and readiness levels are modified to be a cardinal scale (based on an analytic hierarchy process). Integration arcs’ importance are dependent on the connected nodes and the additional integrations arcs connected to those nodes. Lack of integration is not represented by zero, but by a perfect integration maturity value. Naturally, the importance (or weight) of such an arc would be zero. To further explore the impact of grouping subsystems, a multi-objective genetic algorithm is then used to find various clusters or communities that can be optimized for the most representative subsystem SRL. This novel calculation is then benchmarked through simulation and using past defense acquisition program data, focusing on the newly introduced Middle Tier of Acquisition (rapidly field prototypes). The model remains a relatively simple, accessible tool, but at higher fidelity and validated with past data for the program manager to decide major defense acquisition program milestones.

Keywords: readiness, maturity, system, integration

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Authors: Maha Ali Al-Mohaya, Lubna Majed Al-Otaibi, Ebtissam Nassir Al-Bakr, Abdulrahman Al-Asmari

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Objectives: Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. Cytokines play an important role in the pathogenesis and disease progression of OLP. The purpose of this study was to investigate the association of tumor necrosis factor (TNF)-α, TNF-β and interleukin (IL)-10 gene polymorphisms with the OLP risk. Material and Methods: Forty-two unrelated patients with OLP and 211 healthy volunteers were genotyped for TNF-α (-308 G/A), TNF-β (+252A/G), IL-10 (-1082G/A), IL-10 (-819C/T), and IL-10 (-592C/A) polymorphisms. Results: The frequencies of allele A and genotype GA of TNF-α (-308G/A) were significantly higher while allele G and GG genotypes were lower in OLP patients as compared to the controls (P < 0.001). The frequency of GA genotype of TNF-β (+252A/G) was significantly higher in patients than in controls while the AA genotype was completely absent in OLP patients. These results indicated that allele A and genotype GA of TNF-α (-308G/A) as well as the GA genotype of TNF-β (+252A/G) polymorphisms are associated with OLP risk. The frequencies of alleles and genotypes of -1082G/A, -819C/T and -592C/A polymorphisms in IL-10 gene did not differ significantly between OLP patients and controls (P > 0.05). However, haplotype ATA extracted from 1082G/A, -819C/T, -592C/A polymorphisms of IL-10 were more prevalent in OLP patients when compared to controls indicating its possible association with OLP susceptibility. Conclusion: It is concluded that TNF-α (-308G/A), TNF-β (+252A/G) and IL-10 (-1082G/A, -819C/T and -592C/A) polymorphisms are associated with the susceptibility of OLP, thus giving additional support for the genetic basis of this disease. Further studies are required using a larger sample size to confirm this association and determine the prognostic values of these findings.

Keywords: oral lichen planus, cytokines, polymorphism, genetic

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Authors: Aran Abd Al Rahman

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Joubert syndrome regards as a congenital cerebellar ataxia caused by autosomal recessive carried on X chromosome. The disease diagnosed by brain imaging—the so-called molar tooth sign. Neurological signs were present from the neonatal period and include hypotonia progressing to ataxia, global developmental delay, ocular motor apraxia, and breathing dysregulation. These signs are variably associated with multiorgan involvement, mainly of the retina, kidneys, skeleton, and liver. 30 causative genes have been identified so far, all of which encode for proteins of the primary cilium or its apparatus, The purpose of our project was to detect the mutant gene (INPP5E gene) which cause Joubert syndrome. There were many methods used for diagnosis such as MRI and CT- scan and molecular diagnosis by doing ARMS PCR for detection of mutant gene that we were used in this research project. In this research for individual family which reported, the two children with parents, the two children were affected and were carrier.

Keywords: Joubert syndrome, genetic disease, Kurdistan region, Sulaimani

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Authors: Dulal Bhaumik, Fei Jie, Runa Bhaumik, Bikas Sinha

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Human brain is an amazingly complex network. Aberrant activities in this network can lead to various neurological disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease and autism. fMRI has emerged as an important tool to delineate the neural networks affected by such diseases, particularly autism. In this paper, we propose mixed-effects models together with an appropriate procedure for controlling false discoveries to detect disrupted connectivities in whole brain studies. Results are illustrated with a large data set known as Autism Brain Imaging Data Exchange or ABIDE which includes 361 subjects from 8 medical centers. We believe that our findings have addressed adequately the small sample inference problem, and thus are more reliable for therapeutic target for intervention. In addition, our result can be used for early detection of subjects who are at high risk of developing neurological disorders.

Keywords: ABIDE, autism spectrum disorder, fMRI, mixed-effects model

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Authors: Anthara Vivek, Manisha Shukla, Mahesh Narayan, Prakash Narayan

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Sickle cell disease disproportionately affects sub-Saharan Africa and certain tribal populaces in India and has consequently drawn little intertest from Pharma. In sickle cell patients, adhesion of erythrocytes or reticulocytes to one another and the vessel wall results in painful ischemic episodes with few, if any, effective treatments for vaso-occlusive crises. Identification of disease-associated adhesion markers on erythrocytes or reticulocytes might inform the use of more effective therapies against vaso-occlusive crises. Increased expression of one or more of bcam, itga4, cd44, cd47, rap1a, vcam1, or icam4 has been reported in sickle cell subjects. Using the miRNet ontology knowledgebase, peripheral blood interactomes were generated by seeding various combinations of the afore-referenced mRNA. These interactomes yielded an array of miR targets. As examples, targeting hsa-miR-155-5p can potentially neutralize the rap1a-bcam-cd44-itga4-vcam1 erythrocyte/reticulocyte adhesion interactome whereas targeting hsa-miRs-103a-3p or 107 can potentially neutralize adhesion in cells overexpressing icam4-cd47-bcam-itga4-cd36. AM3380 (MIRacle™) is an off-the shelf hsa-miR-155-5p agomiR that can potentially neutralize the rap1a-bcam-cd44-itga4-vcam1 signaling axis. Phlebotomy coupled with transcriptomics represents a potentially feasible and effective precision medicine strategy to mitigate vaso-occlusive crises in sickle cell patients.

Keywords: adhesion, interactome, precision, medicine

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Authors: K. H. Reeta, Bhavana Prasher, Mitali Mukerji, Dhwani Dholakia, Sangeeta Khanna, Archana Vats, Shivam Pandey, Sandeep Seth, Subir Kumar Maulik

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Introduction Research has demonstrated a connection between coronary artery disease (CAD) and genetics. We did a deep literature mining using both bioinformatics and manual efforts to identify the susceptible polymorphisms in coronary artery disease. Further, the study sought to validate these findings in an Asian population. Methodology In first phase, we used an automated pipeline which organizes and presents structured information on SNPs, Population and Diseases. The information was obtained by applying Natural Language Processing (NLP) techniques to approximately 28 million PubMed abstracts. To accomplish this, we utilized Python scripts to extract and curate disease-related data, filter out false positives, and categorize them into 24 hierarchical groups using named Entity Recognition (NER) algorithms. From the extensive research conducted, a total of 466 unique PubMed Identifiers (PMIDs) and 694 Single Nucleotide Polymorphisms (SNPs) related to coronary artery disease (CAD) were identified. To refine the selection process, a thorough manual examination of all the studies was carried out. Specifically, SNPs that demonstrated susceptibility to CAD and exhibited a positive Odds Ratio (OR) were selected, and a final pool of 324 SNPs was compiled. The next phase involved validating the identified SNPs in DNA samples of 96 CAD patients and 37 healthy controls from Indian population using Global Screening Array. ResultsThe results exhibited out of 324, only 108 SNPs were expressed, further 4 SNPs showed significant difference of minor allele frequency in cases and controls. These were rs187238 of IL-18 gene, rs731236 of VDR gene, rs11556218 of IL16 gene and rs5882 of CETP gene. Prior researches have reported association of these SNPs with various pathways like endothelial damage, susceptibility of vitamin D receptor (VDR) polymorphisms, and reduction of HDL-cholesterol levels, ultimately leading to the development of CAD. Among these, only rs731236 had been studied in Indian population and that too in diabetes and vitamin D deficiency. For the first time, these SNPs were reported to be associated with CAD in Indian population. Conclusion: This pool of 324 SNP s is a unique kind of resource that can help to uncover risk associations in CAD. Here, we validated in Indian population. Further, validation in different populations may offer valuable insights and contribute to the development of a screening tool and may help in enabling the implementation of primary prevention strategies targeted at the vulnerable population.

Keywords: coronary artery disease, single nucleotide polymorphism, susceptible SNP, bioinformatics

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Authors: Mahdi Farajzadeh Ajirlou

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The detailed serious adverse effects raised the stresses around the safety of individuals who have gotten COVID-19 vaccines. Numerous verification referrers that disease with COV-19 causes neurological dysfunction in a significant proportion of influenced patients, where these side effects show up seriously amid the disease, and still less is known approximately the potential long-term results for the brain, where the loss of olfaction could be a neurological sign and simple indications of COVID-19. Since publishing effective clinical trial results of mRNA coronavirus disease 2019 (COVID-19) and injecting it to the volunteers in 2020, numerous reports have emerged approximately about cardiovascular complications followed by the mRNA vaccination. Vaccination-associated adenopathy could be a constant imaging finding after the organization of COVID-19 antibodies that will lead to a symptomatic problem in patients with shown or suspected cancer, in whom it may be vague from dangerous nodal inclusion. In spite of all the benefits and viability of the coronavirus infection 2019 (COVID-19) antibodies specified in later clinical trials, a few other post-vaccination side impacts, such as lymphadenopathy (LAP), were observed. Also, numerous variables, including financial conditions, have played a critical part in expanding the number of people with COVID-19 infection and also much more side effects in that country. Amid the Coronavirus widespread, Iran has been experiencing extreme sanctions, which has faced this nation with an extreme financial crisis. Additionally, with COVID-19 widespread, there was a developing concern around the abuse of imaging exams extraordinarily within the pediatric populace, which highlights the issues pointed out by this review.

Keywords: radiology, vaccines, COVID-19, side effect

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Authors: Nozar Kishi, Babak Kamrani, Filmon Habte

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Natural hazards such as earthquakes and tropical storms, are very frequent and highly destructive in Japan. Japan experiences, every year on average, more than 10 tropical cyclones that come within damaging reach, and earthquakes of moment magnitude 6 or greater. We have developed stochastic catastrophe models to address the risk associated with the entire suite of damaging events in Japan, for use by insurance, reinsurance, NGOs and governmental institutions. KCC’s (Karen Clark and Company) catastrophe models are procedures constituted of four modular segments: 1) stochastic events sets that would represent the statistics of the past events, hazard attenuation functions that could model the local intensity, vulnerability functions that would address the repair need for local buildings exposed to the hazard, and financial module addressing policy conditions that could estimates the losses incurring as result of. The events module is comprised of events (faults or tracks) with different intensities with corresponding probabilities. They are based on the same statistics as observed through the historical catalog. The hazard module delivers the hazard intensity (ground motion or wind speed) at location of each building. The vulnerability module provides library of damage functions that would relate the hazard intensity to repair need as percentage of the replacement value. The financial module reports the expected loss, given the payoff policies and regulations. We have divided Japan into regions with similar typhoon climatology, and earthquake micro-zones, within each the characteristics of events are similar enough for stochastic modeling. For each region, then, a set of stochastic events is developed that results in events with intensities corresponding to annual occurrence probabilities that are of interest to financial communities; such as 0.01, 0.004, etc. The intensities, corresponding to these probabilities (called CE, Characteristics Events) are selected through a superstratified sampling approach that is based on the primary uncertainty. Region specific hazard intensity attenuation functions followed by vulnerability models leads to estimation of repair costs. Extensive economic exposure model addresses all local construction and occupancy types, such as post-linter Shinand Okabe wood, as well as concrete confined in steel, SRC (Steel-Reinforced Concrete), high-rise.

Keywords: typhoon, earthquake, Japan, catastrophe modelling, stochastic modeling, stratified sampling, loss model, ERM

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Authors: Tahir Majeed, Michael Handschuh, René Meier

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Rheumatoid arthritis patients have swelling and pain at the joints of the hand. The regions where the patient feels pain also show increased body temperature. Thermal cameras can be used to detect the rise in temperature of the affected regions. To monitor the disease progression of rheumatoid arthritis patients, they must visit the clinic regularly for scanning and examination. After scanning and evaluation, the dosage of the medicine is regulated accordingly. To monitor the disease progression over time, the correlation between the images between different visits must be established. It has been observed that by using low-cost thermal cameras, the thermal measurements do not remain the same over time, even within a single scanning. In some situations, temperatures can vary as much as 2°C within the same scanning sequence. In this paper, it has been shown that although the absolute temperature varies over time, the relative difference between the different regions remains similar. Results have been computed over four scanning sequences and are presented.

Keywords: relative thermal difference, rheumatoid arthritis, thermal imaging, thermal sensors

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Authors: Salam N. Abdo, Orien L. Tulp, George P. Einstein

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The purpose of this exploratory study was to gather the insights into psoriasis etiology, treatment, and patient experience, for developing psoriasis and psoriatic arthritis diagnostic test. Data collection methods consisted of a comprehensive meta-analysis of relevant studies and psoriasis patient survey. Established meta-analysis guidelines were used for the selection and qualitative comparative analysis of psoriasis and psoriatic arthritis research studies. Only studies that clearly discussed psoriasis etiology, treatment, and patient experience were reviewed and analyzed, to establish a qualitative data base for the study. Using the insights gained from meta-analysis, an existing psoriasis patient survey was modified and administered to collect additional data as well as triangulate the results. The hypothesis is that specific types of psoriatic disease have specific etiology and pathophysiologic pattern. The following etiology categories were identified: bacterial, environmental/microbial, genetic, immune, infectious, trauma/stress, and viral. Additional results, obtained from meta-analysis and confirmed by patient survey, were the common age of onset (early to mid-20s) and type of psoriasis (plaque; mild; symmetrical; scalp, chest, and extremities, specifically elbows and knees). Almost 70% of patients reported no prescription drug use due to severe side effects and prohibitive cost. These results will guide the development of psoriasis and psoriatic arthritis diagnostic test. The significant number of medical publications classified psoriatic arthritis disease as inflammatory of an unknown etiology. Thus numerous meta-analyses struggle to report any meaningful conclusions since no definitive results have been reported to date. Therefore, return to the basics is an essential step to any future meaningful results. To date, medical literature supports the fact that psoriatic disease in its current classification could be misidentifying subcategories, which in turn hinders the success of studies conducted to date. Moreover, there has been an enormous commercial support to pursue various immune-modulation therapies, thus following a narrow hypothesis/mechanism of action that is yet to yield resolution of disease state. Recurrence and complications may be considered unacceptable in a significant number of these studies. The aim of the ongoing study is to focus on a narrow subgroup of patient population, as identified by this exploratory study via meta-analysis and patient survey, and conduct an exhaustive work up, aiming at mechanism of action and causality before proposing a cure or therapeutic modality. Remission in psoriasis has been achieved and documented in medical literature, such as immune-modulation, phototherapy, various over-the-counter agents, including salts and tar. However, there is no psoriasis and psoriatic arthritis diagnostic test to date, to guide the diagnosis and treatment of this debilitating and, thus far, incurable disease. Because psoriasis affects approximately 2% of population, the results of this study may affect the treatment and improve the quality of life of a significant number of psoriasis patients, potentially millions of patients in the United States alone and many more millions worldwide.

Keywords: biologics, early diagnosis, etiology, immune disease, immune modulation therapy, inflammation skin disorder, phototherapy, plaque psoriasis, psoriasis, psoriasis classification, psoriasis disease marker, psoriasis diagnostic test, psoriasis marker, psoriasis mechanism of action, psoriasis treatment, psoriatic arthritis, psoriatic disease, psoriatic disease marker, psoriatic patient experience, psoriatic patient quality of life, remission, salt therapy, targeted immune therapy

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Authors: Manik Sharma

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Understanding the anatomy and normal anatomical variations of the lower limb arterial system is undeniably important not only to understand the pathology involving the vessels of the lower limb but also as a part of endovascular intervention and surgical planning in cases that demand them as a part of treatment. There have been very few cases of duplication of SFA cited in the literature, close to six worldwide and this being the seventh case in the world and first to be reported in the Indian population. We incidentally came across this normal variant during US lower limb (US-LL) duplex scan in a patient with claudicating pain in bilateral lower limbs hence suspected of having peripheral vascular disease. It was confirmed on CT-Peripheral Angiography (CT-PA), which was done successively.

Keywords: peripheral vascular disease, claudicating pain, normal anatomical variants, endovascular intervention, duplication, CT-peripheral angiography, duplex scan, Iohexol

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Authors: Metin Kömsöken, Ayşe Güneş Tanır, Onur Karaman

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Usage of high energy charged particles for diagnosis and treatment has been widespread in medicine. The main purpose is to investigate that Bremsstrahlung which occurs by tissue interactions with charged particles should not be neglected. Nuclear stopping power (Bremsstrahlung) was calculated for lung, brain, skin, muscle, bone (cortical) and water targets for the energies of electrons obtained from LINAC used in radiotherapy and of β+ sources used in positron emission tomography (PET). These calculations were done by using the four different analytical functions including classical Bethe-Bloch, Tsoulfanidis, modified Bethe-Bloch and modified Tsoulfanidis equations. It was concluded that obtained results were compatible with that of National Institute of Standards and Technology (NIST-ESTAR).

Keywords: β- emitting source, bremsstrahlung, therapeutic radionuclides, LINAC

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Authors: Simon B. N. Thompson

Abstract:

Retinoblastoma is a rare type of childhood genetic cancer that affects children worldwide. The diagnosis is often missed due to lack of education and difficulty in presentation of the tumor. Frequently, the tumor on the retina is noticed by photography when the red-eye flash, commonly seen in normal eyes, is not produced. Instead, a yellow or white colored patch is seen or the child has a noticeable strabismus. Early detection can be life-saving though often results in removal of the affected eye. Remaining functioning in the healthy eye when the child is young has resulted in super-vision and high or above-average intelligence. Technological advancement of cameras has helped in early detection. Brain imaging has also made possible early detection of neurological diseases and, together with the monitoring of cortisol levels and yawning frequency, promises to be the next new early diagnostic tool for the detection of neurological diseases where cortisol insufficiency is particularly salient, such as multiple sclerosis and Cushing’s disease.

Keywords: cortisol, neurological disease, retinoblastoma, Thompson cortisol hypothesis, yawning

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Authors: James Boag

Abstract:

The needs of people with a diagnosis of dementia and their carers and families are physical, psychosocial, and psychological and begin at the time of diagnosis. There is frequently a lack of emotional support and counselling. Care- giving support is required from the presentation of the first symptoms of dementia until death. Alzheimer's disease begins decades before the clinical symptoms begin to appear, and in many cases, it remains undiagnosed, or diagnosed too late for any possible interventions to have any effect. However, if an incorrect diagnosis is given, it may result in a person being treated, without effect, for a type of dementia they do not have and delaying the interventions they should have received. Being diagnosed with dementia can cause emotional distress to the person, and physical and emotional support is needed, which will become more important as the disease progresses. The severity of the patient's dementia and their symptoms has a bearing of the impact on the carer and the support needed. A lack of insight and /or a denial of the diagnosis, grief, reacting to anticipated future losses, and coping methods to maximise the disease outcome, are things that should be addressed. Because of the stigma, it is important for carers not to lose contact with family and others because social isolation leads to depression and burnout. The impact on a carer's well- being and quality of life can be influenced by the severity of the illness, its type of dementia, its symptoms, healthcare support, financial and social status, career, age, health, residential setting, and relationship to the patient. Carer burnout due to lack of support leads to people diagnosed with dementia being put into residential care prematurely. Often dementia is not recognised as a terminal illness, limiting the ability of the person diagnosed with dementia and their carers to work on advance care planning and getting access to palliative and other support. Many carers have been satisfied with the physical support they were given in their everyday life, however, it was agreed that there was an immense unmet need for psychosocial support, especially after diagnosis and approaching end of life. Providing continuity and coordination of care is important. Training is necessary for providers to understand that every case is different, and they should understand the complexities. Grief, the emotional response to loss, is suffered during the progression of the disease and long afterwards, and carers should continue to be supported after the death of the person they were caring for.

Keywords: dementia, caring, challenges, needs

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Authors: Y. I. Tretyakova, S. G. Shulkina, T. Y. Kravtsova, A. A. Antipova, N. Y. Kolomeets

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The research aimed to assess the functional significance of tumor necrosis factor-alpha (TNF-α) gene polymorphism at the -308G/A (rs1800629) region and vascular endothelial growth factor A (VEGFA) gene polymorphism at the -634G/C (rs 2010963) region in the development of ulcerative colitis (UC), focusing on patients from the Perm region, Russia. We examined 70 UC patients and 50 healthy donors during the active phase of the disease. Our focus was on TNF-α and VEGF concentration in the blood serum, as well as TNF-α and VEGFA gene polymorphisms at the -308G/А and -634G/C regions, respectively. We found that TNF-α and VEGF levels were significantly higher in patients with severe UC and high endoscopic activity compared to those with milder forms of the disease and low endoscopic activity. These tests could serve as additional non-invasive markers for assessing mucosal damage in the large intestine of UC patients. The frequency of allele variations in the TNF-α gene -308G/A (rs1800629) revealed a significantly higher occurrence of the unfavorable homozygote AA in UC patients compared to donors. Additionally, the major allele G and the allele pair GG were more frequent in patients with mild to moderate disease and 1-2 degree of endoscopic activity than in those with severe UC and 3-4 degree of endoscopic activity (χ2=14.19; p=0.000). We also observed a mutant allele A and the unfavorable homozygote AA associated with severe progressive UC. The occurrence of the mutant allele increased the risk of severe UC by 5 times (OR 5.03; CI 12.07-12.21). We did not find any significant differences in the frequency of the CC homozygote (χ2=1.02; p=0.6; OR=1.32) and the mutant allele C of the VEGFA gene -634G/C (rs 2010963) (χ2=0.01; p=0.913; OR=0.97) between groups of UC patients and healthy individuals. However, we detected that the mutant allele C and the unfavorable homozygote CC of the VEGFA gene were associated with more severe endoscopic changes in the colonic mucosa of UC patients (χ2=25,76; р=0,000; OR=0,15). The presence of the mutant allele increased the risk of severe UC by 6 times (OR 6,78; CI 3,13–14,7). We found a direct correlation between TNF-α and VEGFA gene polymorphisms, increased production of the same factors, disease severity, and endoscopic activity (р=0.000). Therefore, the presence of the mutant allele A and homozygote AA of the TNF-α gene at the -308G/A region and the mutant allele C and homozygote CC of the VEGFA gene at the -634G/C region are associated with risks related to an unfavorable clinical course of UC, frequent recurrences, and rapid progression. These findings should be considered when making prognoses regarding the clinical course of the disease and selecting treatment strategies. The presence of the homozygote AA in the TNF-α gene (rs1800629) is considered a sign of genetic predisposition to UC.

Keywords: gene polymorphism, TNF-α, ulcerative colitis, VEGF

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Authors: Moushira Zaki, Wafaa Ezzat, Yasser Elhosary, Omnia Saleh

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Nonalcoholic fatty liver disease (NAFLD) has increased in conjunction with obesity. The accuracy of risk factors for detecting NAFLD in obese adolescents has not undergone a formal evaluation. The aim of this study was to evaluate predictors of NAFLD among Egyptian female obese adolescents. The study included 162 obese female adolescents. All were subjected to anthropometry, biochemical analysis and abdominal ultrasongraphic assessment. Metabolic syndrome (MS) was diagnosed according to the IDF criteria. Significant association between presence of MS and NAFLD was observed. Obese adolescents with NAFLD had significantly higher levels of ALT, triglycerides, fasting glucose, insulin, blood pressure and HOMA-IR, whereas decreased HDL-C levels as compared with obese cases without NAFLD. Receiver–operating characteristic (ROC) curve analysis shows that ALT is a sensitive predictor for NAFLD, confirming that ALT can be used as a marker of NAFLD.

Keywords: obesity, NAFLD, predictors, adolescents, Egyptians, risk factors, prevalence

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Authors: Hitoshi Minakuchi, Izumi Takei, Shu Wakino, Koichi Hayashi, Hiroshi Itoh

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Objectives: Among type 2 diabetics, patients with CKD(chronic kidney disease), insulin resistance, impaired glyconeogenesis in kidney and reduced degradation of insulin are recognized, and we observed different fluctuational patterns of blood sugar between CKD patients and non-CKD patients. On the other hand, non-dipper type blood pressure change is the risk of organ damage and mortality. We performed cross-sectional study to elucidate the characteristic of the fluctuation of blood glucose and blood pressure at insulin-treated diabetic patients with chronic kidney disease. Methods: From March 2011 to April 2013, at the Ichikawa General Hospital of Tokyo Dental College, we recruited 20 outpatients. All participants are insulin-treated type 2 diabetes with CKD. We collected serum samples, urine samples for several hormone measurements, and performed CGMS(Continuous glucose measurement system), ABPM (ambulatory blood pressure monitoring), brain computed tomography, carotid artery thickness, ankle brachial index, PWV, CVR-R, and analyzed these data statistically. Results: Among all 20 participants, hypoglycemia was decided blood glucose 70mg/dl by CGMS of 9 participants (45.0%). The event of hypoglycemia was recognized lower eGFR (29.8±6.2ml/min：41.3±8.5ml/min, P<0.05), lower HbA1c (6.44±0.57%：7.53±0.49%), higher PWV (1858±97.3cm/s：1665±109.2cm/s), higher serum glucagon (194.2±34.8pg/ml：117.0±37.1pg/ml), higher free cortisol of urine (53.8±12.8μg/day：34.8±7.1μg/day), and higher metanephrin of urine (0.162±0.031mg/day：0.076±0.029mg/day). Non-dipper type blood pressure change in ABPM was detected 8 among 9 participants with hypoglycemia (88.9%), 4 among 11 participants (36.4%) without hypoglycemia. Multiplex logistic-regression analysis revealed that the event of hypoglycemia is the independent factor of non-dipper type blood pressure change. Conclusions: Among insulin-treated type 2 diabetic patients with CKD, the events of hypoglycemia were frequently detected, and can associate with the organ derangements through the medium of non-dipper type blood pressure change.

Keywords: chronic kidney disease, hypoglycemia, non-dipper type blood pressure change, diabetic patients

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Authors: Anthony R. Hassan, Jacob A. Gbadeyan

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In this paper, the analysis of a reactive hydromagnetic Poiseuille fluid flow under each of sensitized, Arrhenius and bimolecular chemical kinetics through a channel in the presence of heat source is carried out. An exothermic reaction is assumed while the concentration of the material is neglected. Adomian Decomposition Method (ADM) together with Pade Approximation is used to obtain the solutions of the governing nonlinear non – dimensional differential equations. Effects of various physical parameters on the velocity and temperature fields of the fluid flow are investigated. The entropy generation analysis and the conditions for thermal criticality are also presented.

Keywords: chemical kinetics, entropy generation, thermal criticality, adomian decomposition method (ADM) and pade approximation

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Authors: Atsuko Okazaki, Jurg Ott

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Some genetic diseases (‘digenic traits’) are due to the interaction between two DNA variants. For example, certain forms of Retinitis Pigmentosa (a genetic form of blindness) occur in the presence of two mutant variants, one in the ROM1 gene and one in the RDS gene, while the occurrence of only one of these mutant variants leads to a completely normal phenotype. Detecting such digenic traits by genetic methods is difficult. A common approach to finding disease-causing variants is to compare 100,000s of variants between individuals with a trait (cases) and those without the trait (controls). Such genome-wide association studies (GWASs) have been very successful but hinge on genetic effects of single variants, that is, there should be a difference in allele or genotype frequencies between cases and controls at a disease-causing variant. Frequent pattern mining (FPM) methods offer an avenue at detecting digenic traits even in the absence of single-variant effects. The idea is to enumerate pairs of genotypes (genotype patterns) with each of the two genotypes originating from different variants that may be located at very different genomic positions. What is needed is for genotype patterns to be significantly more common in cases than in controls. Let Y = 2 refer to cases and Y = 1 to controls, with X denoting a specific genotype pattern. We are seeking association rules, ‘X → Y’, with high confidence, P(Y = 2|X), significantly higher than the proportion of cases, P(Y = 2) in the study. Clearly, generally available FPM methods are very suitable for detecting disease-associated genotype patterns. We use fpgrowth as the basic FPM algorithm and built a framework around it to enumerate high-frequency digenic genotype patterns and to evaluate their statistical significance by permutation analysis. Application to a published dataset on opioid dependence furnished results that could not be found with classical GWAS methodology. There were 143 cases and 153 healthy controls, each genotyped for 82 variants in eight genes of the opioid system. The aim was to find out whether any of these variants were disease-associated. The single-variant analysis did not lead to significant results. Application of our FPM implementation resulted in one significant (p < 0.01) genotype pattern with both genotypes in the pattern being heterozygous and originating from two variants on different chromosomes. This pattern occurred in 14 cases and none of the controls. Thus, the pattern seems quite specific to this form of substance abuse and is also rather predictive of disease. An algorithm called Multifactor Dimension Reduction (MDR) was developed some 20 years ago and has been in use in human genetics ever since. This and our algorithms share some similar properties, but they are also very different in other respects. The main difference seems to be that our algorithm focuses on patterns of genotypes while the main object of inference in MDR is the 3 × 3 table of genotypes at two variants.

Keywords: digenic traits, DNA variants, epistasis, statistical genetics

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