Association between Toll-Like Receptor 4 (Thr399Ile and Asp299Gly), Toll-Like Receptor 2 196-174 Deletion Polymorphisms with cryptosporidiosis

Toll-like receptors (TLRs) 2 and 4 specifically recognize lipopolysaccharide motifs on surfaces of microorganisms. Polymorphims in the TLR genes result in structural variations in the proteins, abnormal host-pathogen interactions and hence, altered immune response. Opportunistic parasite Cryptosporidium spp. infects immuno-compromised patients who present with heterogeneous clinical manifestations ranging from mild infection resolving in a few weeks, to severe form characterized by voluminous diarrhoea, prolonged symptoms and recurrences. The present study investigates the role of TLR2 196_174del, TLR4 Asp299Gly and Thr399Ile polymorphisms in pathogenesis of cryptosporidiosis. Stool samples were collected from 210 immuno-compromised (renal transplant recipients and patients with Human immunodeficiency virus infection) both with and without cryptosporidiosis, and 200 healthy subjects for detection of Cryptosporidium spp. Blood samples were also collected from the patients and healthy subjects for genotyping of Δ22 (TLR2 196_174del) polymorphism, A896G (TLR4 Asp299Gly) and C1196T (Thr399Ile) single nucleotide polymorphisms (SNPs) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Cryptosporidium spp. was detected in 70 immunocompromised patients, while it was absent in all the healthy controls. No significant difference was observed in Δ22, A896G and C1196T alleles and genotypes (P > 0.05), between cases and controls. Thus, TLR2 196_174del, TLR4 Asp299Gly and Thr399Ile polymorphisms are not significantly associated with the pathogenesis or progression of cryptosporidiosis, in the Indian population included in the study.

Is non-biological treatment of rheumatoid arthritis as good as biologics?

The management of rheumatoid arthritis(RA) in the past three decades has undergone a paradigm shift from symptomatic relief to a "treat-to-target" approach. This has been possible through use of various conventional and biologic disease modifying anti-rheumatic drugs(DMARDs) which target disease pathogenesis at a molecular level. Cost and infection risk preclude regular use of biologics in resource-constrained settings. In therecent years, evidence has emerged that combination therapy with conventional DMARDs is not inferior to biologics in the management of RA and is a feasible cost-effective option.

Bidirectional link between diabetes mellitus and coronavirus disease 2019 leading to cardiovascular disease:A narrative review

Coronavirus disease 2019(COVID-19)is a global pandemic where several comorbidities have been shown to have a significant effect on mortality.Patients with diabetes mellitus(DM)have a higher mortality rate than non-DM patients if they get COVID-19.Recent studies have indicated that patients with a history of diabetes can increase the risk of severe acute respiratory syndrome coronavirus 2 infection.Additionally,patients without any history of diabetes can acquire newonset DM when infected with COVID-19.Thus,there is a need to explore the bidirectional link between these two conditions,confirming the vicious loop between“DM/COVID-19”.This narrative review presents(1)the bidirectional association between the DM and COVID-19,(2)the manifestations of the DM/COVID-19 loop leading to cardiovascular disease,(3)an understanding of primary and secondary factors that influence mortality due to the DM/COVID-19 loop,(4)the role of vitamin-D in DM patients during COVID-19,and finally,(5)the monitoring tools for tracking atherosclerosis burden in DM patients during COVID-19 and“COVID-triggered DM”patients.We conclude that the bidirectional nature of DM/COVID-19 causes acceleration towards cardiovascular events.Due to this alarming condition,early monitoring of atherosclerotic burden is required in“Diabetes patients during COVID-19”or“new-onset Diabetes triggered by COVID-19 in Non-Diabetes patients”.

Scleroderma: Not an orphan disease any more

Scleroderma(or systemic sclerosis) is a rare disease associated with significant morbidity and mortality.Although previously thought to have a uniformly poor prognosis,the outlook has changed in recent years.We review recent insights into the pathogenesis,clinical features,assessment and management of scleroderma.

Quantifying synovial inflammation:Emerging imaging techniques

Imaging techniques to assess synovial inflammation includes radiography, ultrasound, computed tomography, magnetic resonance imaging(MRI) and recently positron emission tomography. The ideal objective of imaging approaches are to quantify synovial inflammation by capturing features such as synovial hyperplasia, neo-angiogenesis and infiltration of immune cells in the synovium. This may enable clinicians to estimate response to therapy by measuring the improvement in the inflammatory signals at the level of synovium. Ultrasound can provide information regarding thickening of the synovial membrane and can reveal increased synovial blood flow using power Doppler technique. Bone marrow edema and synovial membrane thickness on MRI scan may serve as indicators for arthritis progression. Enhancement of the synovium on dynamic contrast MRI may closely mirror the inflammatory activity in the synovium. Diffusion tensor imaging is an advance MRI approach that evaluates the inflammation related to cell infiltration or aggregation in an inflamed synovium. In this review, we summarize the newer imaging techniques and their developments to evaluate synovial inflammation.