Search results for: disease progression

Authors: Baso Hamdani, Arniati Massinai, Jamaluddin Jompa

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Coral diseases are one of the factors affect reef degradation. This research had analysed the progression rate, incidence, and prevalence of Black Band Disease (BBD) on stony coral (Pachyseris sp.) in relation to the environmental parameters (pH, nitrate, phospate, Dissolved Organic Matter (DOM), and turbidity). The incidence of coral disease was measured weekly for 6 weeks using Belt Transect Method. The progression rate of BBD was measured manually. Furthermore, the prevalence and incidence of BBD were calculated each colonies infected. The relationship between environmental parameters and the progression rate, prevalence and incidence of BBD was analysed by Principal Component Analysis (PCA). The results showed the average of progression rate is 0,07 ± 0,02 cm/ hari. The prevalence of BBD increased from 0,92% - 19,73% in 7 weeks observation with the average incidence of new infected colonies coral 0,2 - 0,65 colony/day The environment factors which important were pH, Nitrate, Phospate, DOM, and Turbidity.

Keywords: progression rate, incidence, prevalence, Black Band Disease, Barranglompo

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Authors: Awol Seid Ebrie

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HIV results as an incurable disease, AIDS. After a person is infected with virus, the virus gradually destroys all the infection fighting cells called CD4 cells and makes the individual susceptible to opportunistic infections which cause severe or fatal health problems. Several studies show that the CD4 cells count is the most determinant indicator of the effectiveness of the treatment or progression of the disease. The objective of this paper is to investigate the progression of the disease over time among patient under HAART treatment. Two main approaches of the generalized multilevel ordinal models; namely the proportional odds model and the nonproportional odds model have been applied to the HAART data. Also, the multilevel part of both models includes random intercepts and random coefficients. In general, four models are explored in the analysis and then the models are compared using the deviance information criteria. Of these models, the random coefficients nonproportional odds model is selected as the best model for the HAART data used as it has the smallest DIC value. The selected model shows that the progression of the disease increases as the time under the treatment increases. In addition, it reveals that gender, baseline clinical stage and functional status of the patient have a significant association with the progression of the disease.

Keywords: nonproportional odds model, proportional odds model, random coefficients model, random intercepts model

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Authors: Michael Aupetit, Mahmoud Al-ismail, Khaled Mohamed

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Cancer is a major public health problem all over the world. Breast cancer has the highest incidence rate over all cancers for women in Qatar making its study a top priority of the country. Human cancer is a dynamic disease that develops over an extended period through the accumulation of a series of genetic alterations. A Darwinian process drives the tumor cells toward higher malignancy growing the branches of a progression tree in the space of genes expression. Although it is not possible to track these genetic alterations dynamically for one patient, it is possible to reconstruct the progression tree from the aggregation of thousands of tumor cells’ genetic profiles from thousands of different patients at different stages of the disease. Analyzing the progression tree is a way to detect pivotal molecular events that drive the malignant evolution and to provide a guide for the development of cancer diagnostics, prognostics and targeted therapeutics. In this work we present the development of a Visual Analytic web platform CanVis enabling users to upload gene-expression data and analyze their progression tree. The server computes the progression tree based on state-of-the-art techniques and allows an interactive visual exploration of this tree and the gene-expression data along its branching structure helping to discover potential driver genes.

Keywords: breast cancer, progression tree, visual analytics, web platform

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Authors: Mequanent Wale Mekonen, Edoardo Otranto, Angela Alibrandi

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Diabetic kidney disease is one of the main microvascular complications caused by diabetes. Several clinical and biochemical variables are reported to be associated with diabetic kidney disease in people with type 2 diabetes. However, their interrelations could distort the effect estimation of these variables for the disease's progression. The objective of the study is to determine how the biochemical and clinical variables in people with type 2 diabetes are interrelated with each other and their effects on kidney disease progression through advanced statistical methods. First, principal component analysis was used to explore how the biochemical and clinical variables intercorrelate with each other, which helped us reduce a set of correlated biochemical variables to a smaller number of uncorrelated variables. Then, ordered logit regression models (cumulative, stage, and adjacent) were employed to assess the effect of biochemical and clinical variables on the order-level response variable (progression of kidney function) by considering the proportionality assumption for more robust effect estimation. This retrospective cross-sectional study retrieved data from a type 2 diabetic cohort in a polyclinic hospital at the University of Messina, Italy. The principal component analysis yielded three uncorrelated components. These are principal component 1, with negative loading of glycosylated haemoglobin, glycemia, and creatinine; principal component 2, with negative loading of total cholesterol and low-density lipoprotein; and principal component 3, with negative loading of high-density lipoprotein and a positive load of triglycerides. The ordered logit models (cumulative, stage, and adjacent) showed that the first component (glycosylated haemoglobin, glycemia, and creatinine) had a significant effect on the progression of kidney disease. For instance, the cumulative odds model indicated that the first principal component (linear combination of glycosylated haemoglobin, glycemia, and creatinine) had a strong and significant effect on the progression of kidney disease, with an effect or odds ratio of 0.423 (P value = 0.000). However, this effect was inconsistent across levels of kidney disease because the first principal component did not meet the proportionality assumption. To address the proportionality problem and provide robust effect estimates, alternative ordered logit models, such as the partial cumulative odds model, the partial adjacent category model, and the partial continuation ratio model, were used. These models suggested that clinical variables such as age, sex, body mass index, medication (metformin), and biochemical variables such as glycosylated haemoglobin, glycemia, and creatinine have a significant effect on the progression of kidney disease.

Keywords: diabetic kidney disease, ordered logit model, principal component analysis, type 2 diabetes

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially the John Cunningham virus (JCV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on JCV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", " John Cunningham virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2019 and 2022 were searched, and 12 articles were chosen, studied, and analyzed. Results: MS patients are candidates for natalizumab therapy, which inhibits lymphocyte migration and increases the risk of progressive multifocal leukoencephalopathy (PML), a rare lytic infection of glial cells caused by JCV. Oligodendrocytes may be the target of JCV infection in the central nervous system (CNS). Conclusion: There is a high expression of JCV during the natalizumab treatment period for MS patients, suggesting that the virus may play a role in the development of MS by inducing an inflammatory state. Therefore, it is necessary to evaluate anti-JCV antibody serum as an important risk factor for the development of PML before deciding on the treatment course for these patients.

Keywords: multiple sclerosis, John Cunningham virus, central nervous system, autoimmunity

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Authors: Behnam Shakerian, Negin Razavi

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The pathogenesis of coronary artery disease is multifactorial. The epicardial fat pad is a localized fat depot lying between the myocardium and the visceral layer of the pericardium. The mechanisms through which epicardial fat pad can cause atherosclerosis are complex. The epicardial fat pad can surround the coronary arteries and contributes to the development and progression of coronary artery disease. Methods: we selected 50 patients who underwent coronary artery angiography for the evaluation of coronary artery disease that results were positive for coronary artery disease. All patients underwent an echocardiographic examination after coronary angiography to measure epicardial fat pad thickness. The epicardial fat pad was defined as an echo-free space between the myocardium's outer wall and the pericardium's visceral layer. Results: The epicardial fat pad was measured on the right ventricle apex in 46 patients. Sixty- five percent of the studied patients were male. The most common vessel with stenosis was the left anterior descending artery. A significant correlation was observed between epicardial fat pad thickness and the severity of coronary artery disease. Discussions: The epicardial fat pad provides a horizon on the pathophysiology of cardiovascular diseases. It directly contributes to the development and progression of coronary artery disease by causing inflammation and endothelial damage. Further investigations are needed to determine whether medical treatment can reduce the mass of epicardial fat pad and can help to improve atherosclerosis. Conclusion: The epicardial fat pad measurement could be used as an indicator of coronary arteries’ atherosclerosis. Therefore, thickness measurement of the epicardial fat pad in the clinical practice could be of assistance in identifying patients at risk and if required, undergoing supplementary diagnosis with coronary angiography.

Keywords: epicardial, fat pad, coronary artery disease, echocardiography

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Authors: Noah Emil Glisik

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Multiple sclerosis (MS) is a chronic, immune-mediated disorder characterized by neurodegenerative processes and a highly variable disease course. Recent research highlights a complex interplay between psychological stress and MS progression, with both acute and chronic stressors linked to heightened inflammatory activity, increased relapse risk, and accelerated disability. This review synthesizes findings from systematic analyses, cohort studies, and neuroimaging investigations to examine how stress contributes to disease dynamics in MS. Evidence suggests that psychological stress influences MS progression through neural and physiological pathways, including dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and heightened activity in specific brain regions, such as the insular cortex. Notably, functional MRI studies indicate that stress-induced neural activity may predict future atrophy in gray matter regions implicated in motor and cognitive function, thus supporting a neurobiological link between stress and neurodegeneration in MS. Longitudinal studies further associate chronic stress with reduced quality of life and higher relapse frequency, emphasizing the need for a multifaceted therapeutic approach that addresses both the physical and psychological dimensions of MS. Evidence from intervention studies suggests that stress management strategies, such as cognitive-behavioral therapy and mindfulness-based programs, may reduce relapse rates and mitigate lesion formation in MS patients. These findings underscore the importance of integrating stress-reducing interventions into standard MS care, with potential to improve disease outcomes and patient well-being. Further research is essential to clarify the causal pathways and develop targeted interventions that could modify the stress response in MS, offering an avenue to address disease progression and enhance quality of life.

Keywords: multiple sclerosis, psychological stress, disease progression, neuroimaging, stress management

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Authors: M. Nosik, I. Rymanova, N. Adamovich, S. Sevostyanihin, K. Ryzhov, Y. Kuimova, A. Kravtchenko, N. Sergeeva, A. Sobkin

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HIV and Tuberculosis (TB) infections each speed the other's progress. HIV-infection increases the risk of TB disease. At the same time, TB infection is associated with clinical progression of HIV-infection. HIV+TB co-infected patients are also at higher risk of acquiring new opportunistic infections. An important feature of disease progression and clinical outcome is the innate and acquired immune responses. HIV and TB, however, have a spectrum of dysfunctions of the immune response. As cytokines play a crucial role in the immunopathology of both infections, it is important to study immune interactions in patients with dual infection HIV+TB. Plasma levels of proinflammatory cytokines IL-2, IFN-γ and immunoregulating cytokines IL-4, IL-10 were evaluated in 75 patients with dual infection HIV+TB, 58 patients with HIV monoinfection and 50 patients with TB monoinfection who were previously naïve for HAART. The decreased levels of IL-2, IFN-γ, IL-4 and IL-10 were observed in patients with dual infection HIV+TB in comparison with patients who had only HIV or TB which means the profound suppression of Th1 and Th2 cytokine secretion. Thus, those cytokines could possibly serve as immunological markers of progression of HIV-infection in patients with TB.

Keywords: HIV, tuberculosis (TB), HIV associated with TB, Th1/ Th2 cytokine expression

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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: Sina Mahdavi

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Multiple sclerosis (MS) is a progressive inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human immunodeficiency virus (HIV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on human HIV infection in MS disease progression. In this study, the keywords "Multiple sclerosis", "Human immunodeficiency virus ", and "Central nervous system" in the databases PubMed, and Google Scholar between 2017 and 2022 were searched and 15 articles were chosen, studied, and analyzed. Revealed histologic signs of "MS-like illness" in the setting of HIV, which comprised widespread demyelination with reactive astrocytes, foamy macrophages, and perivascular infiltration with inflammatory cells, all of which are compatible with MS lesions. Human immunodeficiency virus causes dysfunction of the immune system, especially characterized by hypergammaglobulinemia and chronic activation of B cells. Activation of B cells leads to increased synthesis of immunoglobulin and finally to an excess of free light chains. Free light chains may be involved in autoimmune responses against neurons. There is a high expression of HIV during the course of MS, which indicates the relationship between HIV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of HIV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human immunodeficiency virus, central nervous system, autoimmunity

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Authors: Laura Gantley, Vanessa M. Conn, Stuart Webb, Kirsty Kirk, Marta Gabryelska, Duncan Holds, Brett W. Stringer, Simon J. Conn

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Trinucleotide repeat disorders comprise ~20 severe, inherited human neuromuscular and neurodegenerative disorders, which are a result of an abnormal expansion of repetitive sequences in the DNA. The most common of these, Huntington’s disease, results from the expansion of the CAG repeat region in exon 1 of the HTT gene via an unknown mechanism. Non-coding RNAs have been implicated in the initiation and progression of many diseases; thus, we focus on one circular RNA (circRNA) molecule arising from non-canonical splicing (back splicing) of HTT pre-mRNA. This circRNA and its mouse orthologue were transgenically overexpressed in human cells (SHSY-5Y and HEK293T) and mouse cells (Mb1), respectively. High-content imaging and flow cytometry demonstrated the overexpression of this circRNA reduces cell proliferation, reduces nuclear size independent of cellular size, and alters cell cycle progression. Analysis of protein by western blot and immunofluorescence demonstrated no change to HTT protein levels but altered nuclear-cytoplasmic distribution without impacting the expansion of the HTT repeat region. As these phenotypic and genotypic changes are found in Huntington’s disease patients, these results may suggest that this circRNA may play a functional role in the progression of Huntington’s disease.

Keywords: cell biology, circular RNAs, Huntington’s disease, molecular biology, neurodegenerative disorders

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Authors: Yishu Gong, Liangliang Yang, Jianyu Zhang, Zhengyu Chen, Sihong He, Xusheng Zhang, Wei Zhang

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects millions of people worldwide and is characterized by cognitive decline and behavioral changes. People living with Alzheimer’s disease often find it hard to complete routine tasks. However, there are limited objective assessments that aim to quantify the difficulty of certain tasks for AD patients compared to non-AD people. In this study, we propose to use speech emotion recognition (SER), especially the frustration level, as a potential biomarker for quantifying the difficulty patients experience when describing a picture. We build an SER model using data from the IEMOCAP dataset and apply the model to the DementiaBank data to detect the AD/non-AD group difference and perform longitudinal analysis to track the AD disease progression. Our results show that the frustration level detected from the SER model can possibly be used as a cost-effective tool for objective tracking of AD progression in addition to the Mini-Mental State Examination (MMSE) score.

Keywords: Alzheimer’s disease, speech emotion recognition, longitudinal biomarker, machine learning

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is an inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially Human Herpesvirus 6 (HHV-6), and MS is one potential cause that is not well understood. In this study, we aim to summarize the available data on HHV-6 infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", " Human Herpesvirus 6 ", and "central nervous system" in the databases PubMed and Google Scholar between 2017 and 2022 were searched, and 12 articles were chosen, studied, and analyzed. Results: HHV 6 tends towards TCD 4+ lymphocytes and enters the CNS due to the weakening of the blood-brain barrier due to inflammatory damage. Following the observation that the HHV-6 U24 protein has a seven amino acid sequence with myelin basic protein, which is one of the main components of the myelin sheath, it could cause a molecular mimicry mechanism followed by cross-reactivity. Reactivation of HHV-6 in the CNS can cause the release of proinflammatory cytokines, including TNF-α, leading to immune-mediated demyelination in patients with MS. Conclusion: There is a high expression of endogenous retroviruses during the course of MS, which indicates the relationship between HHV-6 and MS, and that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of HHV-6 may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human herpesvirus 6, central nervous system, autoimmunity

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Authors: Ali Kassem

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Background: In the last few years, factors such as insulin resistance (IR) and hepatic steatosis have been linked to progression of hepatic fibrosis.Patients with chronic liver disease, and cirrhosis in particular, are known to be prone to IR. However, chronic HCV (hepatitis C) infection may induce IR, regardless of the presence of liver cirrhosis. Our aims are to study insulin resistance (IR) assessed by HOMA-IR (Homeostatic Model Assessment Insulin Resistance) as a possible risk factor in disease progression in cirrhotic patients and to evaluate the role of IR in hepatic fibrosis progression. The correlations of HOMA-IR values to laboratory, virological and histopathological parameters of chronic HCV are also examined. Methods: The study included 50 people divided into 30 adult chronic hepatitis C patients diagnosed by PCR (polymerase chain reaction) within previous 6 months and 20 healthy controls. The functional and morphological status of the liver were evaluated by ultrasonography and laboratory investigations including liver function tests and by liver biopsy. Fasting blood glucose and fasting insulin levels were measured and body mass index and insulin resistance were calculated. Patients having HOMA-IR >2.5 were labeled as insulin resistant. Results: Chronic hepatitis C patients with IR showed significantly higher mean values of BMI (body mass index) and fasting insulin than those without IR (P < 0.000). Patients with IR were more likely to have steatosis (p = 0.006), higher necroinflammatory activity (p = 0.05). No significant differences were found between the two groups regarding hepatic fibrosis. Conclusion: HOMA-IR measurement could represent a novel marker to identify the cirrhotic patients at greater risk for the progression of liver disease. As IR is a potentially modifiable risk factor, these findings may have important prognostic and therapeutic implications. Assessment of IR by HOMA-IR and improving insulin sensitivity are recommended in patients with HCV and related chronic liver disease.

Keywords: hepatic fibrosis, hepatitis C virus infection, hepatic steatosis, insulin resistance

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Authors: Stephanie Newman

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Niemann-Pick Type C disease is a rare, usually fatal lysosomal storage disorder. Although clinically characterized by progressive neurodegeneration, there is also evidence of altered innate immune responses such as neuroinflammation that promote disease progression. We have initiated an investigation into whether phagocytosis, an important innate immune activity and the process by which particles are ingested is defective in NPC. Using an in vitro assay, we have shown that NPC macrophages have a deficiency in the phagocytosis of different particles. We plan to investigate the mechanistic basis for impaired phagocytosis, the contribution that this deficiency makes to disease pathology, and whether therapies that have shown in vivo benefit are able to restore phagocytic activity.

Keywords: Niemann Pick Disease C, phagocytosis, innate immunity, lysosomal storage disorder

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Authors: Sujayeva V. A., Karpova I. S., Koslataya O. V., Kolyadko M. G., Russkikh I. I., Vankovich E. A.

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Objective: The goal of this study is to develop a method for the prevention of the progression of heart failure (HF) in patients with post-infarction cardiosclerosis who have suffered coronavirus infection. Methods: 135 patients with post-infarction cardiosclerosis were divided into 2 groups: Group I - patients who had suffered COVID-19 - 85 people, and Group II - patients who had not suffered COVID-19 - 50 people. Patients of group I, depending on the level of N-terminal fragment of natriuretic peptide (NTproBNP), were divided into 2 subgroups - subgroup A - with HF - 40 people, subgroup B - without HF - 45 people. All patients underwent a clinical examination, echocardiography, electrocardiotopography in 60 leads, computed angiography of the coronary arteries, heart magnetic resonance imaging, NTproBNP. Results: In the post-Covid period, in patients with post-infarction cardiosclerosis, remodeling of the left ventricle and right parts of the heart, deterioration of the systolic-diastolic function of both ventricles, increased pressure in the pulmonary artery, progression of coronary artery atherosclerosis, and an increase in the size of myocardial fibrosis were revealed. The consequence of these changes was the progression of heart failure. The developed method of medical prevention made it possible to improve the clinical course of coronary artery disease and prevent the progression of chronic heart failure in patients with post-infarction cardiosclerosis. Conclusions: In patients with post-infarction cardiosclerosis who initially had HF, after 1 year, according to laboratory and instrumental data, a slight decrease in its severity was revealed. In patients with post-infarction cardiosclerosis who did not have HF before COVID-19, HF developed 1 year after the coronavirus disease, which may be due to the identified process of myocardial fibrosis, which dictates the need to prevent the development of HF in patients with post-infarction cardiosclerosis, even those who did not initially have HF. The proposed method of medical prevention made it possible to improve the clinical course of coronary artery disease in patients with post-infarction cardiosclerosis after COVID-19, both in persons with and without HF, when included in the study. A method of medical prevention in people with post-infarction cardiosclerosis after COVID-19 infection, including spironolactone, loop diuretics, empagliflozin, sacubitril/valsartan, helped prevent the progression of HF.

Keywords: elderly, myocardial infarction, COVID-19, prevention

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Authors: Abhaydeep Pandey, Shweta Shukla, Saptamita Goswami, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Sudhanshu Vrati, Arup Banerjee

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Dengue virus infection is now considered as one of the most important mosquito-borne infection in human. The virus is known to promote vascular permeability, cerebral edema leading to Dengue hemorrhagic fever (DHF) or Dengue shock syndrome (DSS). Dengue infection has known to be endemic in India for over two centuries as a benign and self-limited disease. In the last couple of years, the disease symptoms have changed, manifesting severe secondary complication. So far, Delhi has experienced 12 outbreaks of dengue virus infection since 1997 with the last reported in 2014-15. Without specific antivirals, the case management of high-risk dengue patients entirely relies on supportive care, involving constant monitoring and timely fluid support to prevent hypovolemic shock. Nonetheless, the diverse clinical spectrum of dengue disease, as well as its initial similarity to other viral febrile illnesses, presents a challenge in the early identification of this high-risk group. WHO recommends the use of warning signs to identify high-risk patients, but warning signs generally appear during, or just one day before the development of severe illness, thus, providing only a narrow window for clinical intervention. The ability to predict which patient may develop DHF and DSS may improve the triage and treatment. With the recent discovery of high throughput RNA sequencing allows us to understand the disease progression at the genomic level. Here, we will collate the results of RNA-Sequencing data obtained recently from PBMC of different categories of dengue patients from India and will discuss the possible role of deregulated genes and long non-coding RNAs NEAT1 for development of disease progression.

Keywords: long non-coding RNA (lncRNA), dengue, peripheral blood mononuclear cell (PBMC), nuclear enriched abundant transcript 1 (NEAT1), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS)

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Authors: Barsha Saha, Shouvik Chakravarty, Sukanta Ray, Kshaunish Das, Nidhan K. Biswas, Srikanta Goswami

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Pancreatic Ductal Adenocarcinoma is a well-recognised cause of cancer death with a five-year survival rate of about 9%, and its incidence in India has been found to be increased manifold in recent years. Due to delayed detection, this highly metastatic disease has a poor prognosis. Several molecular alterations happen during the progression of the disease from pre-cancerous conditions, and many such alterations could be investigated for their biomarker potential. MicroRNAs have been shown to be prognostic for PDAC patients in a variety of studies. We hereby used NGS technologies to evaluate the role of small RNA changes during pancreatic cancer development from chronic pancreatitis. Plasma samples were collected from pancreatic cancer patients (n=16), chronic pancreatitis patients (n=8), and also from normal individuals (n=16). Pancreatic tumour tissue (n=5) and adjacent normal tissue samples (n=5) were also collected. Sequencing of small RNAs was carried out after small RNAs were isolated from plasma samples and tissue samples. We find that certain microRNAs are highly deregulated in pancreatic cancer patients in comparison to normal samples. A combinatorial analysis of plasma and tissue microRNAs and subsequent exploration of their targets and altered molecular pathways could not only identify potential biomarkers for disease diagnosis but also help to understand the underlying mechanism.

Keywords: small RNA sequencing, pancreatic cancer, biomarkers, tissue sample

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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: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is an inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human endogenous retrovirus (HERV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on HERV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", "Human endogenous retrovirus", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles chosen, studied, and analyzed. Results: In the leptomeningeal cells of MS patients, a retrovirus-like element associated with reverse transcriptase (RT) activity called multiple sclerosis-associated retroviruses (MSRV) has been identified. HERVs are expressed in the human CNS despite mechanisms to suppress their expression. External factors, especially viral infections such as influenza virus, Epstein-Barr virus, and herpes simplex virus type 1, can activate HERV gene expression. The MSRV coat protein is activated by activating TLR4 at the brain surface, particularly in oligodendroglial progenitor cells and macrophages, leading to immune cascades followed by the downregulation of myelin protein expression. The HERV-K18 envelope gene (env) acts as a superantigen and induces inflammatory responses in patients with MS. Conclusion: There is a high expression of endogenous retroviruses during the course of MS, which indicates the relationship between HERV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of endogenous retroviruses may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human endogenous retrovirus, central nervous system, MSRV

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Authors: Kambiz Hassanzadeh, Seyedeh Shohreh Ebrahimi, Shahrbanoo Oryan, Arman Rahimmi, Esmael Izadpanah

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Parkinson’s disease is one of the most prevalent neurodegenerative diseases which occurs in elderly. There are convincing evidences that oxidative stress has an important role in both the initiation and progression of Parkinson’s disease. Thymoquinone (TQ) is shown to have antioxidant and anti-inflammatory properties in invitro and invivo studies. It is well documented that TQ acts as a free radical scavenger and prevents the cell damage. Therefore this study aimed to evaluate the effect of TQ on motor and non-motor symptoms in animal model of Parkinson’s disease. Male Wistar rats (10-12 months) received rotenone (1mg/kg/day, sc) to induce Parkinson’s disease model. Pretreatment with TQ (7.5 and 15 mg/kg/day, po) was administered one hour before the rotenone injection. Three motor tests (rotarod, rearing and bar tests) and two non-motor tests (forced swimming and elevated plus maze) were performed for behavioral assessment. Our results indicated that TQ significantly ameliorated the rotenone-induced motor dysfunction in rotarod and rearing tests also it could prevent the non-motor dysfunctions in forced swimming and elevated plus maze tests. In conclusion we found that TQ delayed the Parkinson's disease induction by rotenone and this effect might be related to its proved antioxidant effect.

Keywords: Parkinson's disease, thymoquinone, motor and non-motor symptoms, neurodegenerative disease

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Authors: Nahashon Mwirigi

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The management of HIV/AIDS is a global challenge, demanding precise tools to predict disease progression and guide tailored treatment. CD4 cell count dynamics, a crucial immune function indicator, play an essential role in understanding HIV/AIDS progression and enhancing patient care through effective modeling. While several models assess disease progression, existing methods often fall short in capturing the complex, non-linear nature of HIV/AIDS, especially across diverse demographics. A need exists for models that balance predictive accuracy with clinical applicability, enabling individualized care strategies based on patient-specific progression rates. This study utilizes patient data from Kenyatta National Hospital (2003–2014) to model HIV/AIDS progression across six CD4-defined states. The Exponential, 2-Parameter Weibull, and 3-Parameter Weibull models are employed to analyze failure rates and explore progression patterns by age and gender. Model selection is based on Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) to identify models best representing disease progression variability across demographic groups. The 3-Parameter Weibull model emerges as the most effective, accurately capturing HIV/AIDS progression dynamics, particularly by incorporating delayed progression effects. This model reflects age and gender-specific variations, offering refined insights into patient trajectories and facilitating targeted interventions. One key finding is that older patients progress more slowly through CD4-defined stages, with a delayed onset of advanced stages. This suggests that older patients may benefit from extended monitoring intervals, allowing providers to optimize resources while maintaining consistent care. Recognizing slower progression in this demographic helps clinicians reduce unnecessary interventions, prioritizing care for faster-progressing groups. Gender-based analysis reveals that female patients exhibit more consistent progression, while male patients show greater variability. This highlights the need for gender-specific treatment approaches, as men may require more frequent assessments and adaptive treatment plans to address their variable progression. Tailoring treatment by gender can improve outcomes by addressing distinct risk patterns in each group. The model’s ability to account for both accelerated and delayed progression equips clinicians with a robust tool for estimating the duration of each disease stage. This supports individualized treatment planning, allowing clinicians to optimize antiretroviral therapy (ART) regimens based on demographic factors and expected disease trajectories. Aligning ART timing with specific progression patterns can enhance treatment efficacy and adherence. The model also has significant implications for healthcare systems, as its predictive accuracy enables proactive patient management, reducing the frequency of advanced-stage complications. For resource limited providers, this capability facilitates strategic intervention timing, ensuring that high-risk patients receive timely care while resources are allocated efficiently. Anticipating progression stages enhances both patient care and resource management, reinforcing the model’s value in supporting sustainable HIV/AIDS healthcare strategies. This study underscores the importance of models that capture the complexities of HIV/AIDS progression, offering insights to guide personalized, data-informed care. The 3-Parameter Weibull model’s ability to accurately reflect delayed progression and demographic risk variations presents a valuable tool for clinicians, supporting the development of targeted interventions and resource optimization in HIV/AIDS management.

Keywords: HIV/AIDS progression, 3-parameter Weibull model, CD4 cell count stages, antiretroviral therapy, demographic-specific modeling

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Authors: H. N. Agiza, M. A. Sohaly, M. A. Elfouly

Abstract:

Parkinson's disease (PD) is a heterogeneous disorder with common age of onset, symptoms, and progression levels. In this paper we will solve analytically the PD model as a non-linear delay differential equation using the steps method. The step method transforms a system of delay differential equations (DDEs) into systems of ordinary differential equations (ODEs). On some numerical examples, the analytical solution will be difficult. So we will approximate the analytical solution using Picard method and Taylor method to ODEs.

Keywords: Parkinson's disease, step method, delay differential equation, two delays

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Authors: Abhaydeep Pandey, Shweta Shukla, Saptamita Goswami, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Sudhanshu Vrati, Arup Banerjee

Abstract:

Background: Long non-coding RNAs (lncRNAs) are the important regulators of gene expression and play important role in viral replication and disease progression. The role of lncRNA genes in the pathogenesis of Dengue virus-mediated pathogenesis is currently unknown. Methods: To gain additional insights, we utilized an unbiased RNA sequencing followed by in silico analysis approach to identify the differentially expressed lncRNA and genes that are associated with dengue disease progression. Further, we focused our study on lncRNAs NEAT1 (Nuclear Paraspeckle Assembly Transcript 1) as it was found to be differentially expressed in PBMC of dengue infected patients. Results: The expression of lncRNAs NEAT1, as compared to dengue infection (DI), was significantly down-regulated as the patients developed the complication. Moreover, pairwise analysis on follow up patients confirmed that suppression of NEAT1 expression was associated with rapid fall in platelet count in dengue infected patients. Severe dengue patients (DS) (n=18; platelet count < 20K) when recovered from infection showing high NEAT1 expression as it observed in healthy donors. By co-expression network analysis and subsequent validation, we revealed that coding gene; IFI27 expression was significantly up-regulated in severe dengue cases and negatively correlated with NEAT1 expression. To discriminate DI from dengue severe, receiver operating characteristic (ROC) curve was calculated. It revealed sensitivity and specificity of 100% (95%CI: 85.69 – 97.22) and area under the curve (AUC) = 0.97 for NEAT1. Conclusions: Altogether, our first observations demonstrate that monitoring NEAT1and IFI27 expression in dengue patients could be useful in understanding dengue virus-induced disease progression and may be involved in pathophysiological processes.

Keywords: dengue, lncRNA, NEAT1, transcriptome

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Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

Abstract:

T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

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Authors: Siamak Shahidi, Nasrin Hashemi-Firouzi, Sara Soleimani-Asl, Alireza Komaki

Abstract:

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory and cognitive performance. Recently, an involvement of the serotonergic system and their receptors are suspected in the AD progression. In the present behavioral study, the effects of BIMU (selective 5-HT4 receptor agonist) on cognition and memory in the rat model of AD was investigated. Material and Methods: The animal model of the AD was induced by intracerebroventricular (Icv) injection of amyloid beta (Aβ) in adult male Wistar rats. Animals were divided into experimental groups included control, sham, Aβ, Aβ +BIMU groups. The treatment substances were icv injected (1 μg/μL) for thirty consecutive days. Then, novel object recognition (NOR) and passive avoidance learning (PAL) tests were applied to investigate memory and cognitive performance. Results: Aβ decrease the discrimination index of NOR test. Also, it increases the time spent in the dark compartment during PAL test, as compared with sham and control groups. In addition, compared to Aβ groups, BIMU significantly increased the discrimination index of NOR test and decreased the time spent in the dark compartment of PAL test. Conclusion: These findings suggest that 5-HT4 receptor activation prevents progression of memory and cognitive impairment in a rat model of AD.

Keywords: Alzheimer disease, cognition, memory, serotonin receptors

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Authors: Sina Mahdavi, Mahdi Asghari Ozma

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Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human Varicella-zoster virus (VZV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on VZV retrovirus infection in MS disease progression. For this study, the keywords "Multiple sclerosis", " Human Varicella-zoster virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles were chosen, studied, and analyzed. Analysis of the amino acid sequences of HNRNPA1 with VZV proteins has shown a 62% amino acid sequence similarity between VZV gE and the PrLD/M9 epitope region (TNPO1 binding domain) of mutant HNRNPA1. A heterogeneous nuclear ribonucleoprotein (hnRNP), which is produced by HNRNPA1, is involved in the processing and transfer of mRNA and pre-mRNA. Mutant HNRNPA1 mimics gE of VZV as an antigen that leads to autoantibody production. Mutant HnRNPA1 translocates to the cytoplasm, after aggregation is presented by MHC class I, followed by CD8 + cells. Of these, antibodies and immune cells against the gE epitopes of VZV remain due to the memory immune response, causing neurodegeneration and the development of MS in genetically predisposed individuals. VZV expression during the course of MS is present in genetically predisposed individuals with HNRNPA1 mutation, suggesting a link between VZV and MS, and that this virus may play a role in the development of MS by inducing an inflammatory state. Therefore, measures to modulate VZV expression may be effective in reducing inflammatory processes in demyelinated areas of MS patients in genetically predisposed individuals.

Keywords: multiple sclerosis, varicella-zoster virus, central nervous system, autoimmunity

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Authors: Emil Sakharov, Alex Zotov, Ilkin Osmanov, Oleg Shelest, Aleksander Troitskiy, Robert Khabazov

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Objective: Since 2015, our center has been actively implementing methods of surgical correction of atrial fibrillation, in particular, in patients with coronary heart disease. The study presents a comparative analysis of the late postoperative period in patients with coronary artery bypass grafting and atrial fibrillation. Methods: The study included 150 patients with ischemic heart disease and atrial fibrillation for the period from 2015 to 2021. Patients were divided into 2 groups. The first group is represented by patients with ischemic heart disease and atrial fibrillation who underwent coronary bypass surgery and surgical correction of atrial fibrillation (N=50). The second group is represented by patients with ischemic heart disease and atrial fibrillation who underwent only myocardial revascularization (N=100). Patients were comparable in age, gender, and initial severity of the condition. Among the patients in group 1 there were 82% were men, while in the second group, their number was 75%. Among the patients of the first group, there were 36% with persistent atrial fibrillation, 20% with long-term persistent atrial fibrillation. In the second group, 10% with persistent atrial fibrillation and 17% with long-term persistent atrial fibrillation. Results: Average follow-up for groups 1 and 2 amounted to 47 months. There were no complications in group 1, such as bleeding and stroke. There was only 1 patient in group 1, who had died from cardiovascular disease. Freedom of atrial fibrillation was in 82% without AADs therapy. In group 2 there were 8 patients who had died from cardiovascular diseases and total freedom of atrial fibrillation was in 35% of patients, among which 42.8% had additional AADs therapy. Follow-up data are presented in Table 2. Progression of heart failure was observed in 3% in group 1 and 7% in group 2. Combined endpoints (recurrence of AF, stroke, progression of heart failure, myocardial infarction) were achieved in 16% in group 1 and 34% in group 2, respectively. Freedom from atrial fibrillation without antiarrhythmic therapy was 82% for group 1 and 35% for group 2. In the first group, there is a more pronounced decrease in heart failure rates. Deaths from cardiovascular causes were recorded in 2% for group 1 and 7% for group 2. Conclusion: Surgical treatment of atrial fibrillation helps to reduce adverse complications in the late postoperative period and contributes to the regression of heart failure.

Keywords: atrial fibrillation, coronary artery bypass grafting, ischaemic heart disease, heart failure

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Authors: Frank Boris Feutmba Keutchou, Saurelle Fabienne Bieghan Same, Verelle Elsa Fogang Pokam, Charles Ursula Metapi Meikeu, Angel Marilyne Messop Nzomo, Ousman Tamgue

Abstract:

Infectious diseases are one of the most important causes of morbidity and mortality worldwide. These diseases are caused by micro-pathogenic organisms, such as bacteria, viruses, parasites, and fungi. Heritable changes in gene expression that do not involve changes to the underlying DNA sequence are referred to as epigenetics. Emerging evidence suggests that epigenetic mechanisms are important in the emergence and progression of infectious diseases. Pathogens can manipulate host epigenetic machinery to promote their own replication and evade immune responses. The Human Genome Project has provided new opportunities for developing better tools for the diagnosis and identification of target genes. Several epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA expression, have been shown to influence infectious disease outcomes. Understanding the epigenetic mechanisms underlying infectious diseases may result in the progression of new therapeutic approaches focusing on host-pathogen interactions. The goal of this study is to show how different infectious agents interact with host cells after infection.

Keywords: epigenetic, infectious disease, micro-pathogenic organism, phenotype

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Authors: Jeffey George, Varghese Thomas

Abstract:

Background and Objectives: PHG is an important source of gastrointestinal bleeding in patients with portal hypertension. Aim: To assess the progression to severe portal hypertensive gastropathy(PHG) in patients with cirrhosis who were treated with maximum tolerated dose of propranalol, after variceal eradication to grade II or below. Methods: Cirrhotic patients(child A and B) presenting with upper gastrointestinal bleeding with endoscopic findings of mild or no PHG were followed up over 6 months after variceal eradication to assess the progression to severe PHG. Included patients were randomised to either maximum tolerated doses of propranalol (group A) or to no treatment (group B). Primary end point of the study were the development of gastrointestinal bleed, evidence of hepatic decompensation and death. Progression to severe PHG were compared between the two groups. Results: 56 patients (49 males) were enrolled (group A = 28, group B = 28). 8 patients were excluded from final analysis (gi bleed=5, encephalopathy=2,HCC=1 including 4 deaths).3 patients were lost to follow-up, and 1 developed intolerance to propranalol. Mean dose of propranalol used was 60 mg per day. Progression to severe PHG in the fundus over 6 months was 23.8% in group A versus 15.8 % in group B (p = 0.52). Severe PHG was noted in body in 14.3% in group A versus 21.1% in group B (p = 0.57). 23.8 % in group A had progression to severe PHG compared with 15.8 % in group B (p =0.52). There was no statistically significant difference in the progression of PHG between the two groups(p=0.43). Conclusion: In this short term study propranalol was found not to prevent the progression to severe portal hypertensive gastropathy in cirrhotic patients who had undergone endotherapy for esophageal varices.

Keywords: propranalol, portal hypertensive gastropathy, cirrhotic patients, gastroenterology

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