Overview of Rheumatoid Arthritis and Scientific Understanding of the Disease.

Rheumatoid arthritis (RA), a chronic inflammatory autoimmune disorder, is characterised by persistent synovial inflammation, erosion of bones and cartilage, leading to joint destruction. Clinical manifestations are morning stiffness, pain in shoulder, neck and pelvic girdle, loss of mobility with fever, fatigue, malaise, loss of body weight, and development of rheumatoid nodules. Environmental and genetic factors are important contributors in its susceptibility. Association between RA and diet, cigarette smoking, hormones, alcohol, microbiota, infection, and coffee have also been reported. To diagnose patients with RA, American college of rheumatology (ACR, 2010) criteria, developed by European league against rheumatism (EULAR). Inflammation produced in RA patients is due to cell-mediated immune response. The rheumatoid synovium consists of a large number of CD4+ T cells suggesting pathogenic nature of T cells in this disorder. B-cells may also participate in the pathogenesis by several means such as autoantibodies, by instigation of T-cells through expression of co-stimulatory molecules, by generating pro-inflammatory and anti-inflammatory cytokines and by organisation of other inflammatory cells. The conventional management of RA usually focuses over reducing pain and limiting the disability by medical therapies which include a number of classes of agents such as non-steroidal anti-inflammatory drugs (NSAIDs), non-biological and biological agents, disease-modifying anti rheumatic drugs (DMARDs), immunosuppressants, and corticosteroids. However, only proper rehabilitation can promote the objective to achieve the joint functionality and ease of motion which improves independence as well as quality of life in patient suffering from Rheumatoid Arthritis.

The study of healthcare facility utilization problems faced by pregnant women in urban north India.

OBJECTIVES: Sub-Saharan African countries account for nearly half of maternal deaths, and Southern Asian countries are second in the 85% of deaths that occur worldwide. Despite this fact, there is a rapid enhancement in the number of skilled health workers. There has been a sharp increase of 53% in 1990 and 61% in 2007 in trained birth attendant utilization shows that attention is being paid to the management of labor services. But surprisingly, still, the births take place without the assistance of trained health personnel in Southern Asian countries and Sub-Saharan Africa. The objective of this study is the assessment of barriers to health care facility utilization and its management concerning labor problems in urban North India. METHODS: A sample of "300" pregnant urban women was taken for study and analysis. A convenience sampling method was used. The factor analysis was applied for the interpretation and analysis of the data. RESULTS: It was found that there were inadequacies in services as well as unawareness of services in almost all urban areas among pregnant women. CONCLUSIONS: The tremendous increase in the cost of services and corrupt behavior among the service providers rampantly found in the urban locations, inaccessibility of proper means of communication and also economic backwardness and low literacy became the impediment to the utilization of maternal healthcare services in North-India.

COVID-19 infection in pregnancy: a review of existing knowledge.

The world has been coping up with the grave pandemic of COVID-19 since its inception into the human race in December, 2019. By entering the host through the spike (S) glycoprotein, it paves way for its own survival and multiplication. Respiratory tract being the point of entry causes pulmonary compromise and leads to development of ARDS. Having non-specific clinical features that resemble flu makes the clinical diagnosis much more difficult. Pregnancy being an immunocompromised and a hypercoagulable state is prone to be a high-risk group for COVID-19. This study is an attempt to understand the maternal and fetal outcomes in COVID-19 and the vertical transmissibility of the virus. Evidence suggests that the contribution of COVID-19 is not very significant in maternal morbidity and mortality. However, due to some factors such as the immunological response in the mother, certain complications may arise in the neonate in the post-natal period. No vertical transmission of the virus has been reported yet. However, the management remains crucial as two lives are at stake. Some of the precautionary measures that can be implemented to prevent COVID-19 can be segregation of medical services from that of the general population in settings of outpatient care, inpatient care and labor room care. Also, triaging the patients into low risk, moderate risk and high risk can aid in faster delivery of health-care facilities to the pregnant and the newborn.

Interleukin10-1082 A/G polymorphism: Allele frequency, correlation with disease markers, messenger RNA and serum levels in North Indian rheumatoid arthritis patients.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder of unknown etiology. IL-10 stimulates B cell survival and is involved in antibody isotype switching. The serum IL-10 levels are increased in RA patients. Ethnicity influences polymorphisms in cytokine genes. Therefore, this study was designed to explore possible association, if any, between polymorphism of IL10-1082 A/G, serum cytokine levels, inflammatory markers and gene expression in RA patients of North India. METHODOLOGY: A total of 187 RA patients classified according to American college of rheumatology 2010 criteria and 214 controls were included in the study. Levels of serum IL-10 and inflammatory markers were estimated by ELISA. PCR-RFLP was used to analyze IL10-1082 A/G polymorphism. Quantitative real time PCR was used to measure the mRNA expression of IL-10 gene. RESULTS: The serum inflammatory markers were significantly higher in RA patients. Circulating IL-10 levels were positively and significantly correlated with RF (r = 0.28), anti-CCP (r = 0.26), CRP (r = 0.17) and mRNA expression levels (r = 0.59) among RA patients. Homozygous mutant variant (GG) and heterozygous mutant variant (AG) were associated with patients of RA (OR = 2.87 and 1.55, p < 0.05) as compared to controls. The association still persisted when the heterozygous and homozygous mutants (AG + GG) were clubbed together (OR = 1.67, p < 0.05). The mRNA expression of IL-10 was found to be 3.63 folds higher (housekeeping gene, ß-actin) and 2.42 folds higher (housekeeping gene, 18S rRNA) in RA patients as compared to controls. CONCLUSION: The results indicate that IL10-1082 A/G polymorphism is associated with genetic susceptibility/predisposition to RA in North Indian population.

Association of polymorphic variants in IL1B gene with secretion of IL-1ß protein and inflammatory markers in north Indian rheumatoid arthritis patients.

The proinflammatory cytokine interleukin-1beta (IL-1ß) is a key mediator of inflammation which affects cell proliferation and differentiation. IL-1ß is considered to contribute to the pathophysiology of rheumatoid arthritis (RA). Polymorphisms in cytokine genes are highly influenced by ethnicity. Hence, in this study polymorphism of the IL1B-511(C/T) within promoter region was analyzed by using polymerase chain reaction-restriction fragment length Polymorphism (PCR-RFLP) in 187 RA patients and 214 controls. The prevalence of different genotypes and allelic frequency distribution was compared in RA patients and controls. Levels of inflammatory markers and serum levels of IL-1ß were estimated by ELISA The serum inflammatory markers levels were significantly higher in RA patients as compared to controls (RF=127.3±21.3U/mL, Anti-CCP=17.8±8.3U/mL, CRP=17.86±7.1mg/L and IL-1ß=21.25±4.19pg/mL in RA patients p<0.01). The frequency of heterozygous mutant (C/T) and homozygous mutant (T/T) variants were significantly higher in RA patients as compared to controls and the odds ratios by logistic regression were (OR=2.2, p<0.001) and (OR=3.21, p<0.01) respectively. The association persisted on combining the heterozygous mutant and homozygous mutant (CT+TT) together as compared to controls (OR=2.39; p<0.001). Positive and significant (p<0.05) correlation of circulating IL-1ß levels with RF (r=0.232), anti-CCP (r=0.207) and CRP (r=0.166) among RA patients were found. The levels of anti-CCP were significantly higher in homozygous mutant variants (TT) as well as the heterozygous mutant variants (C/T) in comparison to the wild variants (CC) (p<0.01). The results of this study reveal that mutant allele (T) of IL1B-511 promoter SNP tends to be associated with elevated anti-CCP and IL-1ß levels as observed in RA patients and hence disease susceptibility.

Tumor necrosis factor-α -308 polymorphism in North Indian rheumatoid arthritis patients and association with mRNA and serum TNF-α.

Rheumatoid arthritis (RA) is a severely disabling chronic autoimmune disorder that leads to progressive inflammation of the joints and surrounding tissues. TNF-α, a potent proinflammatory cytokine, plays a pivotal role in the pathogenesis of RA. The endogenous formation of TNF-α may be influenced by TNF-α promoter polymorphisms. Hence, the present study was designed to explore any possible association between genetic polymorphism of TNF-α -308 G/A, messenger RNA (mRNA) expression, serum levels of TNF-α, and inflammatory markers in North Indian RA patients. A total of 214 controls and 187 RA patients were recruited according to the revised American College of Rheumatology 2010 criteria. TNF-α -308 G/A genetic polymorphism within promoter region was analyzed by using PCR-RFLP. Levels of inflammatory markers and serum TNF-α were estimated by ELISA. The mRNA expression of TNF-α gene was measured by quantitative real-time PCR. Higher levels of autoantibodies (RF and anti-CCP) were present in RA patients as compared to controls. We found a positive and significant correlation of circulating TNF-α levels with RF (r = 0.18), anti-CCP (r = 0.16), and mRNA expression of TNF-α gene (r = 0.57) in RA patients. The mRNA expression levels of TNF-α was 4.5-fold higher in patients with RA as compared to controls. The heterozygous mutant variants (G/A) and homozygous mutant variants (A/A) were found to be significantly associated with RA as compared to control (OR = 1.52 and 3.02, respectively). Our observations illustrated a significant association of allele -308 A TNF-α with progression of RA. Significant and positive correlation of TNF-α levels with mRNA expression and inflammatory marker levels suggests that serum TNF-α may be a susceptibility marker for RA.