Progressive Inflammatory Condition Research Articles

From joint to heart: Cardiovascular implications of rheumatoid arthritis

Rheumatoid arthritis is a commonly encountered autoimmune disease and a progressive chronic inflammatory condition that often leads to permanent joint damage. Systemic inflammation in rheumatoid arthritis is linked to various comorbid conditions such as interstitial lung disease, osteoporosis, metabolic syndrome, cardiovascular disease, infections, malignancies, cognitive dysfunction, depression, and fatigue, which can increase morbidity and mortality in rheumatoid arthritis patients. Approximately 36% of patients report worse health and limitations in daily activities, while nearly 30% require more assistance with personal care compared to individuals without rheumatoid arthritis. Epidemiological data from 1990 to 2017 show an incidence of rheumatoid arthritis of 246.6 per 100,000 people aged 33-54 years, with prevalence in women 2-3 times higher. In Southeast Asia, the incidence is 89 per 100,000 in individuals aged 13-22 years, while in Indonesia, it is estimated at around 5-7.5 per 100,000 population. Cardiovascular disease is the primary cause of mortality in rheumatoid arthritis patients, with myocardial infarction being the major contributor. The pathogenesis of rheumatoid arthritis is still complex and involves immunological processes that occur long before joint inflammation symptoms appear, including genetic modifications and environmental factors that lead to deimination and joint disturbances. Cardiovascular manifestations, particularly myocardial infarction, occur due to an atherosclerotic process triggered by rheumatoid antibody complexes. Given the higher cardiovascular risk in rheumatoid arthritis patients, early detection and awareness of these manifestations are crucial for better management.

Association Between Severe Periodontitis and Cognitive Decline in Older Adults.

(1) Background: Periodontal disease, a progressive inflammatory condition, disrupts the oral microbiome and releases inflammatory cytokines, leading to systemic issues, including cognitive decline. This study investigates the association between severe periodontitis and cognitive decline, exploring the role of alkaline phosphatase (ALP), an enzyme linked to systemic inflammation, as an effect modifier. (2) Methods: We analyzed cross-sectional data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). Severe periodontitis was defined using the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics (AAP) case definition. A weighted multivariable logistic regression model assessed the association between severe periodontitis and cognitive decline. An interaction term examined ALP's role as an effect modifier. (3) Results: This study included 1265 participants aged 65 and older. After adjusting for confounders, each one-point increase in cognitive function score was associated with a 2% decrease in the odds of severe periodontitis (OR = 0.98; 95% CI = 0.97-0.99; p = 0.008). ALP was a significant effect modifier in the relationship between severe periodontitis and cognitive decline. (4) Conclusions: This study, using a representative U.S. adult population aged 65 and over, suggests that lower cognitive performance correlates with higher likelihood of severe periodontitis. ALP enhances the association between severe periodontitis and cognitive decline.

A Prevalence-Based Study to Estimate Cost of Illness of Rheumatoid Arthritis in a Tertiary Care Hospital in India

Background: Rheumatoid arthritis (RA) is a chronic progressive inflammatory condition with high cost of management and significant impact on the patient and healthcare system. Hence, there is a need to estimate and analyze the economic impact of RA. Materials and Methods: It was a cross-sectional prospective follow-up single-center study at a tertiary care hospital conducted over a period of 02 years and 06 months from September 2019 to February 2022 after ethical committee clearance. Results: A total of 189 RA patients were included after excluding 15 patients. The male-to-female ratio was 0.687. The mean age of the study population was 44.74 ± 5.2 years. The mean yearly average cost of management of RA was Rs 29155.1 ± 18234.1, of which 49.6% was direct medical, 19.4% was direct non-medical, and 31% was indirect costs. Of average direct medical costs, cost toward non-steroidal anti-inflammatory drugs (NSAIDs) was 3.1%; conventional disease-modifying antirheumatic drugs (DMARDs) was 36.3%; and laboratory, radiology investigations, and consultations was 6.4%, 1.48%, and 12.3%, respectively. Factors, such as longer duration of treatment, use of biologic DMARDs, loss of productive workdays, extraarticular manifestations, and management of complications, were associated with higher cost of treatment of RA. Conclusions: This study quantifies the economic burden of the RA by measuring costs incurred toward all aspects of the patient’s life including the indirect costs due to loss of workdays. The knowledge of cost will help in financial management by patients and healthcare providers.

Multi-modal transcriptomic analysis reveals metabolic dysregulation and immune responses in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD), a progressive inflammatory condition of the airways, emerges from the complex interplay between genetic predisposition and environmental factors. Notably, its incidence is on the rise, particularly among the elderly demographic. Current research increasingly highlights cellular senescence as a key driver in chronic lung pathologies. Despite this, the detailed mechanisms linking COPD with senescent genomic alterations remain elusive. To address this gap, there is a pressing need for comprehensive bioinformatics methodologies that can elucidate the molecular intricacies of this link. This approach is crucial for advancing our understanding of COPD and its association with cellular aging processes. Utilizing a spectrum of advanced bioinformatics techniques, this research delved into the potential mechanisms linking COPD with aging-related genes, identifying four key genes (EP300, MTOR, NFE2L1, TXN) through machine learning and weighted gene co-expression network analysis (WGCNA) analyses. Subsequently, a precise diagnostic model leveraging an artificial neural network was developed. The study further employed single-cell analysis and molecular docking to investigate senescence-related cell types in COPD tissues, particularly focusing on the interactions between COPD and NFE2L1, thereby enhancing the understanding of COPD's molecular underpinnings. Leveraging artificial neural networks, we developed a robust classification model centered on four genes—EP300, MTOR, NFE2L1, TXN—exhibiting significant predictive capability for COPD and offering novel avenues for its early diagnosis. Furthermore, employing various single-cell analysis techniques, the study intricately unraveled the characteristics of senescence-related cell types in COPD tissues, enriching our understanding of the disease's cellular landscape. This research anticipates offering novel biomarkers and therapeutic targets for early COPD intervention, potentially alleviating the disease's impact on individuals and healthcare systems, and contributing to a reduction in global COPD-related mortality. These findings carry significant clinical and public health ramifications, bolstering the foundation for future research and clinical strategies in managing and understanding COPD.

Effect of allyl isothiocyanate on 4-HNE induced glucocorticoid resistance in COPD and the underlying mechanism

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory condition, and its clinical management primarily targets bronchodilation and anti-inflammatory therapy. However, these treatments often fail to directly address the progression of COPD, particularly its associated glucocorticoid (GC) resistance. This study elucidates the mechanisms underlying GC resistance in COPD and explores the therapeutic potential of allyl isothiocyanate (AITC) in modulating MRP1 transport. We assessed the levels of the oxidative stress product 4-HNE, HDAC2 protein, inflammatory markers, and pulmonary function indices using animal and cell models of GC-resistant COPD. The cascade effects of these factors were investigated through interventions involving AITC, protein inhibitors, and dexamethasone (DEX). Cigarette smoke-induced oxidative stress in COPD leads to the accumulation of the lipid peroxidation product 4-HNE, which impairs HDAC2 protein activity and diminishes GC-mediated anti-inflammatory sensitivity due to disrupted histone deacetylation. AITC regulates MRP1, facilitating the effective efflux of 4-HNE from cells, thereby reducing HDAC2 protein degradation and restoring dexamethasone sensitivity in COPD. These findings elucidate the mechanism of smoking-induced GC resistance in COPD and highlight MRP1 as a potential therapeutic target, as well as the enormous potential of AITC for combined GC therapy in COPD, promoting their clinical applications.

Utilizing a balloon sheath and miniprobe for diagnostic endoscopic ultrasound in eosinophilic esophagitis: a case series

BackgroundEndoscopic ultrasound (EUS) is a unique example of POCUS, which allows the gastroenterologist to discuss subepithelial pathology immediately after an endoscopy. The challenges that are encountered to create an acoustic interface by adding free water during the endoscopy may be curtailing the full utilization of EUS during endoscopic procedures. Eosinophilic esophagitis (EoE) is a progressive inflammatory condition whose morbidity is related to esophageal wall remodeling. However, in clinical practice, in clinical guidelines, and in many trials, EoE outcomes are based on esophageal eosinophilia and symptoms. Hence, a method to identify and quantitate the thickening of the esophageal wall, could contribute to the management of this disease.ResultsA modification of the approach employed to perform EUS during bronchoscopy was developed. An EUS miniprobe was positioned inside of a water filled balloon sheath. This technique permitted rapid and reproducible images acquisition of the total esophageal wall and its sublayers (mucosa, and submucosa + submucosa, which permitted derivation of the muscle layer). The presented series describes the results from 22 consecutive EoE patients. A full set of measurements from both the mid and distal esophagus were achieved in all EoE patients in an average time of less than 10 minutes.ConclusionsThis pilot study supports further investigations evaluating this economical, convenient, and safe technique to follow EoE patients. In addition, this approach could be potentially employed in all patients who are found to have subepithelial gastrointestinal pathology during routine endoscopic procedures.

Crohn's Disease: Radiological Answers to Clinical Questions and Review of the Literature.

Background: Crohn's disease (CD) is a chronic, progressive inflammatory condition, involving primarily the bowel, characterized by a typical remitting-relapsing pattern. Despite endoscopy representing the reference standard for the diagnosis and assessment of disease activity, radiological imaging has a key role, providing information about mural and extra-visceral involvement. Methods: Computed Tomography and Magnetic Resonance Imaging are the most frequently used radiological techniques in clinical practice for both the diagnosis and staging of CD involving the small bowel in non-urgent settings. The contribution of imaging in the management of CD is reported on by answering the following practical questions: (1) What is the best technique for the assessment of small bowel CD? (2) Is imaging a good option to assess colonic disease? (3) Which disease pattern is present: inflammatory, fibrotic or fistulizing? (4) Is it possible to identify the presence of strictures and to discriminate inflammatory from fibrotic ones? (5) How does imaging help in defining disease extension and localization? (6) Can imaging assess disease activity? (7) Is it possible to evaluate post-operative recurrence? Results: Imaging is suitable for assessing disease activity, extension and characterizing disease patterns. CT and MRI can both answer the abovementioned questions, but MRI has a greater sensitivity and specificity for assessing disease activity and does not use ionizing radiation. Conclusions: Radiologists are essential healthcare professionals to be involved in multidisciplinary teams for the management of CD patients to obtain the necessary answers for clinically relevant questions.

Metabolomic insights in advanced cardiomyopathy of chronic chagasic and idiopathic patients that underwent heart transplant

Heart failure (HF) studies typically focus on ischemic and idiopathic heart diseases. Chronic chagasic cardiomyopathy (CCC) is a progressive degenerative inflammatory condition highly prevalent in Latin America that leads to a disturbance of cardiac conduction system. Despite its clinical and epidemiological importance, CCC molecular pathogenesis is poorly understood. Here we characterize and discriminate the plasma metabolomic profile of 15 patients with advanced HF referred for heart transplantation – 8 patients with CCC and 7 with idiopathic dilated cardiomyopathy (IDC) – using gas chromatography/quadrupole time-of-flight mass spectrometry. Compared to the 12 heart donor individuals, also included to represent the control (CTRL) scenario, patients with advanced HF exhibited a metabolic imbalance with 21 discriminating metabolites, mostly indicative of accumulation of fatty acids, amino acids and important components of the tricarboxylic acid (TCA) cycle. CCC vs. IDC analyses revealed a metabolic disparity between conditions, with 12 CCC distinctive metabolites vs. 11 IDC representative metabolites. Disturbances were mainly related to amino acid metabolism profile. Although mitochondrial dysfunction and loss of metabolic flexibility may be a central mechanistic event in advanced HF, metabolic imbalance differs between CCC and IDC populations, possibly explaining the dissimilar clinical course of Chagas’ patients.

Preclinical evaluation of topical emulgel containing fixed dose allo-herbal combination in imiquimod induced psoriasis

Psoriasis is a well-known autoimmune, progressive inflammatory condition having long-term impact on the patient's physical and psychological well-being with worldwide prevalence. The available allopathic and herbal medicines have their own merits and demerits. Allopathic drugs may produce potent beneficial as well as adverse effects while alone herbal drugs may exert slow and less potent effects. Hence the current study attempted to prepare and evaluate fixed dose combination of allo-herbal emulgel in order to minimize adverse effects and improve beneficial effects during the treatment of psoriasis. This study used a well-established, robust, and validated model (Imiquimod (IMQ)) for psoriasis induction. Emulgel was formulated and tested using phytochemical and physicochemical methods. The anti-psoriatic and anti-inflammatory activities of the prepared emulgel were investigated. In addition, percent release and in vivo absorption were done to ensure adequate release and absorption of emulgel content. Progress of psoriasis induction and treatment was analyzed by morphological and histopathological studies.The formulated emulgel was found to comply with the standard physicochemical test with the desired release pattern. Morphological and histological data showed induction of psoriasis using the IMQ model, and significant improvement was observed after emulgel treatment. All formulations were discovered to significantly reduce formalin-induced inflammation.The present study provided the rationale for the combination of C. amada and P. pinnata with salicylic acid. The selected allo-herbal combination and optimized dosage form are stable, biocompatible, and effective anti-inflammatory and anti-psoriatic with potentially fewer side effects.

Endoscopic Management of Crohn’s Disease Strictures

Crohn’s disease is a chronic, progressive inflammatory condition characterised by gastrointestinal tract inflammation and extra-intestinal manifestations. Some patients may develop stricturing disease, which may either be of inflammatory, fibrotic or post-anastamotic aetiologies. The management of fibrostenosis is challenging, necessitating preventative strategies and a multidisciplinary approach to its diagnosis and management once established. Although several treatment options are currently used in the management of strictures, there are currently no targeted anti-fibrotic therapies. Endoscopically, there are several modalities that can be employed in the symptomatic patient including balloon dilatation and stenting. In this article we will briefly discuss the pathophysiology and investigations with focus centred around endoscopic management of Crohn’s strictures, before suggesting a strategy to employ when approaching these cases.

Pemetrexed ameliorates Con A-induced hepatic injury by restricting M1 macrophage activation

Autoimmune hepatitis (AIH), characterized by immune-driven liver destruction and cytokine production, is a progressive inflammatory liver condition that may progress to hepatic cirrhosis or tumors. However, the underlying mechanism is not well understood, and the treatment options for this disease are limited. Pemetrexed (PEM), a clinically used anti-folate drug for treating various tumors, was found to inhibit the nuclear factor (NF)-κB signaling pathways that exert an important role in the development of AIH. Here, we investigated the impact of PEM on immune-mediated hepatic injuries using a murine model of Concanavalin A (Con A)-induced hepatitis, a well-established model for AIH.Mice received intraperitoneal PEM injections 3 times at 12-hour intervals, and two hours later, they were challenged with Con A. Liver samples and serum were collected after 10 h. The results indicate that PEM significantly improved mouse survival rates and lowered serum transaminase levels. Moreover, PEM effectively alleviated oxidative stress, reduced histopathological liver damage, and mitigated hepatocyte apoptosis. Notably, it reduced the activation of M1-type macrophages in the liver. The expression of proinflammatory cytokines and genes associated with M1 macrophages, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-12, IL-1β, and inducible nitric oxide synthase (iNOS), was also decreased. Finally, the results indicated that PEM regulates M1 macrophage activation by modulating the NF-κB signaling pathways.Overall, these results demonstrate that PEM effectively guards against immune-mediated hepatic injuries induced by Con A by inhibiting M1 macrophage activation through the NF-κB signaling pathways and indicate the potential of PEM as a practical treatment option for AIH in clinical settings.

Periodontal Disease and Its Association with Metabolic Syndrome-A Comprehensive Review.

Periodontal disease is a complex and progressive chronic inflammatory condition that leads to the loss of alveolar bone and teeth. It has been associated with various systemic diseases, including diabetes mellitus and obesity, among others. Some of these conditions are part of the metabolic syndrome cluster, a group of interconnected systemic diseases that significantly raise the risk of cardiovascular diseases, diabetes mellitus, and stroke. The metabolic syndrome cluster encompasses central obesity, dyslipidemia, insulin resistance, and hypertension. In this review, our objective is to investigate the correlation between periodontal disease and the components and outcomes of the metabolic syndrome cluster. By doing so, we aim to gain insights into the fundamental mechanisms that link each systemic condition with the metabolic syndrome. This deeper understanding of the interplay between these conditions and periodontal disease can pave the way for more effective treatments that take into account the broader impact of managing periodontal disease on the comprehensive treatment of systemic diseases, and vice versa.

NT-proBNP in Different Patient Groups of COPD: A Systematic Review and Meta-Analysis.

NT-proBNP, a peptide biomarker synthesized and secreted by cardiomyocytes in response to cardiac load, has gained attention in recent years for its potential role in respiratory diseases. Chronic Obstructive Pulmonary Disease (COPD), a chronic and progressive inflammatory condition affecting the respiratory system, is frequently associated with comorbidities involving the cardiovascular system. Consequently, the aim of this systematic review and meta-analysis was to evaluate the variations in NT-proBNP levels across distinct patient groups with COPD and establish a foundation for future investigations into the precise clinical significance of NT-proBNP in COPD. The search databases for this study were conducted in PubMed, Excerpt Medica database (Embase), Web of Science (WOS), and Cochrane Library databases. Databases were searched for studies on the predictive value of NT-proBNP in adult COPD patients. A total of 29 studies (8534 participants) were included. Patients with stable COPD exhibit elevated levels of NT-proBNP [standardized mean difference(SMD) [95CI%]=0.51 [0.13,0.89]; p=0.0092]. COPD patients with predicted forced expiratory volume in 1 s (FEV1) < 50% exhibit significantly elevated levels of NT-proBNP compared to those with FEV1 ⩾50%[SMD [95CI%]=0.17 [0.05,0.29]; p=0.0058]. NT-proBNP levels were significantly higher in acute exacerbations (AECOPD) compared to patients with stable COPD [SMD [95CI%]=1.18 [0.07,2.29]; p=0.037]. NT-proBNP levels was significantly higher in non-survivors than in survivors of hospitalised AECOPD patients [SMD [95CI%]=1.67 [0.47,2.88]; p=0.0063]. Both COPD patients with pulmonary hypertension(PH) [SMD [95CI%]=0.82 [0.69,0.96]; p<0.0001] and chronic heart failure(CHF) [SMD [95CI%]=1.49 [0.96,2.01]; p<0.0001] showed higher NT-proBNP level. NT-proBNP, a biomarker commonly used in clinical practice to evaluate cardiovascular disease, demonstrates significant variations in different stages of COPD and during the progression of the disease. The fluctuations in NT-proBNP levels could be indicative of the severity of pulmonary hypoxia and inflammation and cardiovascular stress among COPD patients. Therefore, assessing NT-proBNP levels in COPD patients can aid in making informed clinical decisions.

STAT3/NF‑κB decoy oligodeoxynucleotides inhibit atherosclerosis through regulation of the STAT/NF‑κB signaling pathway in a mouse model of atherosclerosis.

Atherosclerosis is a progressive chronic inflammatory condition that is the cause of most cardiovascular and cerebrovascular diseases. The transcription factor nuclear factor‑κB (NF‑κB) regulates a number of genes involved in the inflammatory responses of cells that are critical to atherogenesis, and signal transducer and activator of transcription (STAT)3 is a key transcription factor in immunity and inflammation. Decoy oligodeoxynucleotides (ODNs) bind to sequence‑specific transcription factors and limit gene expression by interfering with transcription invitro and invivo. The present study aimed to investigate the beneficial functions of STAT3/NF‑κB decoy ODNs in liposaccharide (LPS)‑induced atherosclerosis in mice. Atherosclerotic injuries of mice were induced via intraperitoneal injection of LPS and the mice were fed an atherogenic diet. Ring‑type STAT3/NF‑κB decoy ODNs were designed and administered via an injection into the tail vein of the mice. To investigate the effect of STAT3/NF‑κB decoy ODNs, electrophoretic mobility shift assay, western blot analysis, histological analysis with hematoxylin and eosin staining, Verhoeff‑Van Gieson and Masson's trichrome staining were performed. The results revealed that STAT3/NF‑κB decoy ODNs were able to suppress the development of atherosclerosis by attenuating morphological changes and inflammation in atherosclerotic mice aortae, and by reducing pro‑inflammatory cytokine secretion through inhibition of the STAT3/NF‑κB pathway. In conclusion, the present study provided novel insights into the antiatherogenic molecular mechanism of STAT3/NF‑κB decoy ODNs, which may serve as an additional therapeutic intervention to combat atherosclerosis.

Management of Pancreatic Calculi in Chronic Pancreatitis: A Review Article.

Chronic pancreatitis is a slow, irreversible, and progressive inflammatory condition with abdominal pain, loss of parenchyma, fibrosis, and calculus formation. It also causes loss of exocrine and endocrine function. Gallstones and alcohol is the most frequent cause of chronic pancreatitis. It is also caused by other factors, including oxidative stress, fibrosis, and repeated incidence of acute pancreatitis. Chronic pancreatitis is followed by several sequelae, one of them being formation of calculi in the pancreas. The formation of calculi can occur in the main pancreatic duct, branches of the duct, and parenchyma. The cardinal sign of chronic pancreatitis is pain caused by obstruction of pancreatic ducts and its branches leading to ductal hypertension resulting in pain. The main aim of endotherapy includes pancreatic duct decompression. The management options vary based on the type and size of the calculus. The treatment of choice for small-sized pancreatic calculi is endoscopic retrograde cholangiopancreatography (ERCP) followed by sphincterotomy and extraction. The large-sized calculi need fragmentation before extraction, which is done by extracorporeal shock wave lithotripsy (ESWL). Surgery can be an option for patients having severe pancreatic calculi if endoscopic therapy fails. For diagnostic purposes, imaging plays a very important role. The treatment options remain complex if the radiological and laboratory findings overlap. Due to advancements in diagnostic imaging, treatment options have become precise and helpful. It can significantly lower the quality of life along with immediate and long-term problems that pose a serious risk to life. This review comprises the various management options available for removing calculi following chronic pancreatitis, including surgical, endoscopic, and medical therapy.

The Efficacy and Safety of Subcutaneous Ixekizumab for the Treatment of Axial Spondylarthritis: A Systematic Review and Meta-Analysis.

Axial spondylarthritis (axSpA) is a progressive inflammatory condition that is treated with various management options. Interleukin-17A (IL-17A)inhibitors are a novel therapeutic option that demonstrates both efficacy and safety. This systematic review and meta-analysis evaluated the effectiveness of ixekizumab and its safety compared to a placebo. Medline, ScienceDirect, EBSCO, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched. We included randomized control trials (RCTs) that assessed the efficacy and safety of ixekizumab versus the placebo. The GRADE (Gradingof Recommendations, Assessment, Development, and Evaluations) assessment was utilized to evaluate the certainty of evidence. The revised Cochrane risk of bias tool for randomized trials was used to assess the risk of bias. Four RCTs (n=1016) met the eligibility criteria. All included studies had a low risk of bias. Significant improvements in the Assessment of Spondylarthritis International Society response for 40% improvement (ASAS40) (RR = 2.39, 95% CI 1.72-3.31, P < 0.01, I2 = 23%), Ankylosing Spondylitis Disease Activity Score (ASDAS) (SMD= -9.28 95% CI -12.31- (-6.25), P < 0.01, I2=97%), andSpondylarthritis Research Consortium of Canada (SPRACC score) (SMD= -5.82 95% CI -7.16- (-4.47), P < 0.01, I2=94%) were noted in comparison to placebo. Regarding safety, there was an insignificant increase in risk for serious adverse events (SAEs) (RR = 1.19, 95% CI 0.45-3.14, P = 0.73, I2 = 0%). Additionally, significant nonserious adverse events (NSAEs) (RR = 1.54, 95% CI 1.19-1.99, P = 0.001, I2 = 0%) were noted for the ixekizumab arm. No mortality events were detected in both arms. Ixekizumab, which demonstrates significant improvement in all efficacy endpoints, is a promising management option for axSpA patients who fail non-steroidal anti-inflammatory drugs (NSAIDs) therapy. However, the significant risk of developing adverse events hinders its utilization. More high-quality RCTs with larger sample sizes and prolonged follow-up periods are warranted to further assess this treatment option.

Environmental risk factors for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic, progressive immune-mediated inflammatory condition of the gastrointestinal tract. Environmental risk factors play a role in developing either type of IBD, Crohn's disease and ulcerative colitis; although the exact mechanism is still unknown. Herein, we review environmental risks from early life exposures, lifestyle and hygiene, vaccinations, surgeries, exposure to drugs and gastrointestinal pathogens that may increase the risk of developing IBD.

Coevolution of HTLV-1-HBZ, Tax, and proviral load with host IRF-1 and CCNA-2 in HAM/TSP patients

Background HTLV-1-associated myelopathy (HAM/TSP) is a progressive neurodegenerative inflammatory condition of HTLV-1 infection. Viral-host interactions are a significant contributor to the symptoms of HTLV-1-associated diseases. Therefore, in this study, the expression of the main regulatory viral factors and proviral load (PVL) and two host transcription molecules were evaluated in HAM/TSP patients. Materials and methods The study population included 17 HAM/TSP patients, 20 asymptomatic carriers (ACs), and 19 healthy controls (HCs). RNA and DNA were extracted from PBMCs for assessment of the gene expressions and PVL assessment using RT-qPCR and TaqMan method. Results HTLV-1-PVL was higher in HAM/TSPs (395.80±99.69) than ACs (92.92±29.41) (P=0.001). The Tax expression in HAM/TSPs (7.8±5.7) was strongly higher than ACs (0.06±0.04) (P=0.02), while HTLV-1-HBZ was only increased around three times in HAM/TSPs (3.17), compared to ACs (1.20) and not significant. The host IRF1 expression in HAM/TSPs (0.4±0.31) was higher than ACs (0.09±0.05) (P=0.02) and also HCs (0.16±0.07) (P=0.5), but lower in ACs than HCs (p=0.01). Although, in HAM/TSPs (0.13±0.09) and ACs (0.03±0.02) CCNA-2 expression was statistically fewer than HCs (0.18±0.06) (P=0.03, P=0.001, respectively), in HAM/TSP was higher than ACs (P=0.1), but did not meet a 95% confidence interval. Conclusion The study showed that HTLV-1-PVL and Tax, along with host IRF-1, could be considered biomarkers in HAM/TSP development. Furthermore, IRF-1, as an essential transcription factor, can be considered a pivotal target in HAM/TSPs treatment.

Genome-Wide Association Analysis for Chronic Superficial Keratitis in the Australian Racing Greyhound.

Chronic superficial keratitis (CSK) is a progressive inflammatory condition of the eye (cornea) that can cause discomfort and blindness. Differential disease risk across dog breeds strongly suggests that CSK has a genetic basis. In addition to genetic risk, the occurrence of CSK is exacerbated by exposure to ultraviolet light. Genome-wide association analysis considered 109 greyhounds, 70 with CSK and the remainder with normal phenotype at an age over four years. Three co-located variants on CFA18 near the 5′ region of the Epidermal Growth Factor Receptor (EGFR) gene were associated with genome-wide significance after multiple-test correction (BICF2P579527, CFA18: 6,068,508, praw = 1.77 × 10−7, pgenome = 0.017; BICF2P1310662, CFA18: 6,077,388, praw = 4.09 × 10−7, pgenome = 0.040; BICF2P160719, CFA18: 6,087,347, praw = 4.09 × 10−7, pgenome = 0.040) (canFam4)). Of the top 10 associated markers, eight were co-located with the significantly associated markers on CFA18. The associated haplotype on CFA18 is protective for the CSK condition. EGFR is known to play a role in corneal healing, where it initiates differentiation and proliferation of epithelial cells that in turn signal the involvement of stromal keratocytes to commence apoptosis. Further validation of the putative functional variants is required prior to their use in genetic testing for breeding programs.

A171 EXPLORING PATIENT PERSPECTIVES ON A 12-WEEK, ONLINE STRESS REDUCTION INTERVENTION IN INFLAMMATORY BOWEL DISEASE

BackgroundInflammatory bowel disease (IBD) which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic relapsing-remitting or progressive inflammatory condition. In addition to physical symptoms, individuals with IBD experience uncertainty about their future, social isolation, and increased psychological stress. Conventional medical and surgical IBD treatment does not adequately address the the impact of psychological stress. Online stress reduction interventions may therefore be useful adjuncts to standard medical therapies for IBD. The Peace Power Pack (PPP) trial was a 12-week RCT testing a stress reduction intervention with two core components: (i) a yoga, breathwork and meditation video, and (ii) a behavior-change facilitation informed by cognitive behavioral therapy.AimsThe aims of this qualitative study, which was carried out alongside the PPP trial was to: (i) explore the experience of living with IBD, (ii) understand the impacts of the PPP program, and (iii) identify potential improvements to the program.MethodsUpon completion of the 12-week RCT, all intervention participants were invited to participate in semi-structured interviews. A qualitative descriptive approach was used. Interviews were analyzed through a theoretical thematic analysis process, whereby transcripts were coded, and codes then grouped into larger categories and themes.ResultsOf the 56 participants interviewed, 52% had CD and 48% had UC. Participants ranged in age from 23 to 73 years, were predominantly female (70%) and had been diagnosed with IBD 14.3 years ago. Three main themes (Table 1) were identified: (i) IBD as a source of stress and uncertainty, (ii) understanding the positive impacts of the stress reduction program, and (iii) suggested strategies to enhance program desirability. IBD was described as causing uncertainty, significant disruptions to daily activities, and stress. The online program was associated with a perceived reduction in IBD symptom burden, an increased ability to manage daily and disease-associated stressors, and a more positive mindset. Variation in program content and fostering connections with others in the IBD community were identified as potential strategies to enhance future programming.ConclusionsThis study highlights the power of the patient voice to deepen our understanding of the impact of IBD, and the potential benefit of an online stress reduction program including suggestions for iterative refinement.Table 1. Themes identified with sample quotationsThemeSample quoteIBD as a sources of stress & uncertainty“It’s stress from the fact that no one really knows the cause. No one really knows the cure and it’s maybe going to get worse over time”.Understanding the positive impacts of the PPP programI catch myself . . . I’m much more mindful of what’s going on stress wise . . . it changed how I look at stress and how I cope with it.Enhancing program desirabilityI wanted to talk to other people in the program who had similar life situations to me. Like working full-time, having young children at home . . . to share strategies they were using to make time to do this.Funding AgenciesUniversity of Alberta Hospital Foundation, the American College of Gastroenterology and the Inflammation, Microbiome, and Alimentation: Gastrointestinal and Neuropsychiatric Effects (IMAGINE) Network CIHR grant