Profiling system-wide variations and similarities between Rheumatic Heart Disease and Acute Rheumatic Fever-A pilot analysis.

Rheumatic heart disease (RHD) continues to affect developing countries with low income due to the lack of resources and effective diagnostic techniques. Understanding the genetic basis common to both the diseases and that of progression from its prequel disease state, Acute Rheumatic Fever (ARF), would aid in developing predictive biomarkers and improving patient care. To gain system-wide molecular insights into possible causes for progression, in this pilot study, we collected blood transcriptomes from ARF (5) and RHD (5) patients. Using an integrated transcriptome and network analysis approach, we identified a subnetwork comprising the most significantly differentially expressed genes and most perturbed pathways in RHD compared to ARF. For example, the chemokine signaling pathway was seen to be upregulated, while tryptophan metabolism was found to be downregulated in RHD. The subnetworks of variation between the two conditions provide unbiased molecular-level insights into the host processes that may be linked with the progression of ARF to RHD, which has the potential to inform future diagnostics and therapeutic strategies. We also found a significantly raised neutrophil/lymphocyte ratio in both ARF and RHD cohorts. Activated neutrophils and inhibited Natural Killer cell gene signatures reflected the drivers of the inflammatory process typical to both disease conditions.

Quantitative analysis of retinal microvascular changes in prediabetic and diabetic patients.

PURPOSE: To evaluate and correlate retinal microvascular changes in prediabetic and diabetic patients with functional and systemic parameters. METHODS: Optical coherence tomography angiography (OCTA) was performed on all subjects after medical evaluation and laboratory investigations for blood sugar, glycosylated hemoglobin, and others. Automated quantification of vascular indices of the superficial plexus were analyzed. RESULTS: Hundred and eleven persons (222 eyes) were grouped into prediabetic (PDM) (60 eyes), diabetic without retinopathy (NDR) (56 eyes), diabetic with retinopathy (DR) (66 eyes), and healthy controls (CTR) (40 eyes). The superficial retinal capillary plexus showed no significant changes in the prediabetic and NDR groups; however, central foveal thickness (CFT) was significantly reduced in PDM (P = 0.04). The circularity of the foveal avascular zone (FAZ) (P = 0.03) and the vessel density (VD) (P = 0.01) showed significant reduction from PDM to NDR. All vascular parameters were significantly reduced in DR and correlated with disease severity. The CFT correlated significantly with FAZ area. The VD and perfusion density were seen to correlate significantly with HbA1c and contrast sensitivity. The visual acuity was significantly correlated with the FAZ. Logistic regression revealed VD [OR 20.42 (7.9-53)] and FAZ perimeter [OR 9.8 (4.2-23.2)] as the strongest predictors of DR. CONCLUSION: The changes in OCTA can help predict onset of DR. FAZ changes are seen in early stages and are correlated well with systemic parameters, making it an easy target to monitor and screen for severity of DR. Significant reduction in the CFT in PDM suggests that neuronal damage precedes vascular changes.

Early structural and functional neurovascular changes in the retina in the prediabetic stage.

PURPOSE: This study was undertaken to investigate the neurovascular changes in the retina of prediabetic subjects. METHODS: Subjects enroled in a prospective study were separated into prediabetic and normal control groups based on their glycosylated haemoglobin (HbA1C) levels, fasting and postprandial blood sugar levels and glucose tolerance test. All the subjects underwent detailed ophthalmic evaluation, which included fundus examination, fundus photography, optical coherence tomography angiography (OCTA), and multifocal electroretinogram (mfERG). Comparisons were done between the groups using the Wilcoxon signed rank test. RESULTS: The median age was 48 years for the normal controls (n = 40), and 49.5 years for prediabetic subjects (n = 45) (p = 0.306). There was no difference in the vision, contrast sensitivity, thickness of the ganglion cell complex or the foveal avascular zone parameters between the groups. But the central foveal thickness and subfoveal choroidal thickness were significantly reduced in prediabetics (p < 0.01). The mfERG showed significant differences in the amplitude. The average amplitude was 35 ± 12 nv/deg2 in the normals and 29 ± 11 nv/deg2 in the prediabetics (p = 0.003). A weak positive correlation was noted between the mfERG and vascular parameters in the prediabetic group. CONCLUSIONS: The prediabetic stage reveals earliest functional neuronal changes in the retina. The neuronal function seems to be affected much earlier than clinically appreciable structural changes in the ganglion cell complex and precedes vascular changes in the retina.

Investigating the role of microRNA-27a gene polymorphisms and its interactive effect with risk factors in gastrointestinal cancers.

Gastrointestinal (GI) cancers are known to have a high incidence worldwide and require an early diagnosis to successfully treat them, providing higher survival rates and better quality of life for the patients. MicroRNA-27a is a well-known oncogene that plays a significant role in various GI cancers. It is known to upregulate the expression of numerous oncogenes leading to cancer progression. The miR-27a harbors two polymorphisms rs895819 and rs11671784 which alter the disease susceptibility by interfering with the maturation and expression of miR-27a. In the current study, we aimed to investigate the role played by these polymorphisms in cancers of the GI tract. We conducted a case-control study with 210 GI cancer cases and 210 cancer-free controls to analyze the effect of these polymorphisms. The rs895819 polymorphism was genotyped using PCR-RFLP, and rs11671784 was genotyped on a MassARRAY platform. The association analysis failed to bring out any significant association of the polymorphisms with GI cancer risk. However, genotype-phenotype interaction analysis revealed that the rs895819 was found to increase the risk GI cancers along with the presence of risk factors such as socioeconomic status, diabetes mellitus, hypertension, alcohol consumption, and tobacco chewing.