👤 Tirth Dave

CNS tumors are a significant cause of death in the adolescent and young adult (AYA; age 15-39 years) population; however, these patients often lack standardized treatments. In Canada, we have established national multidisciplinary virtual AYA CNS tumor board rounds (national rounds) to improve and standardize care. From November 2021 to June 2024, 185 AYA patients with CNS tumors were presented from centers nationwide, including 138 patients with glioma. Before case presentation, 5.1% of patients with glioma were taking targeted agents or were enrolled in clinical trials. However, after national rounds, 72.6% of patients with pediatric-type glioma and 45.9% of patients with adult-type glioma were recommended clinical trials and/or targeted agents. Among the 44 patients with glioma who had received radiation therapy before national rounds, only 14 were recommended further radiation. Cumulatively, 68.9% of patients analyzed received a treatment recommendation that represented a change in clinical management compared with their previous treatments. Concurrently, we performed molecular review of 174 AYA CNS tumors during the study time frame. Using TruSight, we identified gene fusions involving Our results suggest that national rounds with centralized molecular review can direct AYA patients with CNS tumors toward targeted agents and clinical trials, while deferring radiation therapy. Taken together, our work details an ongoing effort to improve and standardize care of AYA patients with CNS tumors in Canada. Show less

Cardiovascular disease (CVD) is a leading cause of global mortality. Early intervention and prevention of CVD depend on accurately predicting the risk of CVD. This study aimed to investigate the association between the TyG index and the risk of coronary heart disease (CHD), congestive heart failure (CHF), heart attack (HA), stroke, and hypertension (HTN) among patients without diabetes in the United States. In this retrospective, cross-sectional study, we used data from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2020. We conducted several regression analysis models and calculated the sensitivity and specificity of (TyG) index for predicting the onset of CHD, CHF, HA, stroke, and HTN. A total of 10,937 individuals without diabetes participated in our study. Individuals with a TyG index greater than 8.96 displayed significant increasing in various parameters, including BMI, systolic/diastolic blood pressure, total cholesterol, LDL, and Apo-B levels (p < 0.001). Almost all regression models ensured that a higher TyGI value was associated with higher odds of having CHD, CHF, HA, stroke, and HTN, which patients with a TyGI value higher than 8.96 have odds ratios of 2.24-5.58 for CHD, 1.68-4.42 for stroke, 2.45-3.77 for HA and 1.75-3.93 for HTN comparing than patients with a TyGI value lower than 8.11 (p-value < 0.05).We evaluated the predictive value of the TyG index for each endpoint, obtaining the following area under the curve (AUC) values: 54.75% for CHF (95% CI: 0.542-0.614), 52.32% for stroke (95% CI: 0.529-0.584), 55.67% for HA (95% CI: 0.595-0.646), 55.59% for HTN (95% CI: 0.574-0.597), and 50.31% for CHD (95% CI: 0.592-0.646). The TyG index showed a strong correlation with cardiovascular risk factors in individuals without diabetes, however it was a poor predictor of almost studied cardiovascular diseases. Show less

This work involved the preparation of pristine and iron nanoparticle-loaded biochar from a water chestnut shell to remove diclofenac sodium (DCF) containing effluent of pharmaceutical origin. To create suitable forecasting equations for the modelling of the DCF adsorption onto the adsorbent, response surface methodology (RSM) was used. The parameters, e.g. pH, adsorbent mass, DCF concentration and contact time, were used for the modeling of adsorption. The RSM model predicts that for 98.0% DCF removal, the ideal conditions are pH 6, an adsorbent dose of 0.5 g L Show less

Pseudoexfoliation (PEX) syndrome is an age-related progressive disease of the extracellular matrix with ocular manifestations. PEX is clinically diagnosed by the presence of extracellular exfoliative deposits on the anterior surface of the ocular lens. PEX syndrome is a major risk factor for developing glaucoma, the leading cause of irreversible blindness in the world, and is often associated with the development of cataract. PEX reportedly coexists with Alzheimer disease and increases the risk of heart disease and stroke. PEX material deposited on the anterior surface of the ocular lens is highly proteinaceous, complex, and insoluble, making deciphering the protein composition of the material challenging. Thus, to date, only a small proportion of the protein composition of PEX material is known. The aim of this study was to decipher the protein composition of pathological PEX material deposited on the ocular lens in patients and advance the understanding of pathophysiology of PEX syndrome. Liquid-chromatography and tandem mass spectrometry (LC-MS/MS) was employed to discover novel proteins in extracts of neat PEX material surgically isolated from patients (n = 4) with PEX syndrome undergoing cataract surgery. A sub-set of the identified proteins was validated with immunohistochemistry using lens capsule specimens from independent patients (n=3); lens capsules from patients with cataract but without PEX syndrome were used as controls (n=4). Expression of transcripts of the validated proteins in the human lens epithelium was analyzed with reverse transcription PCR (RT-PCR). Functional relationships among the proteins identified in this study and genes and proteins previously implicated in the disease were bioinformatically determined using InnateDB. Peptides corresponding to 66 proteins, including ten proteins previously known to be present in PEX material, were identified. Thirteen newly identified proteins were chosen for validation. Of those proteins, 12 were found to be genuine components of the material. The novel protein constituents include apolipoproteins (APOA1 and APOA4), stress response proteins (CRYAA and PRDX2), and blood-related proteins (fibrinogen and hemoglobin subunits), including iron-free hemoglobin. The gene expression data suggest that the identified stress-response proteins and hemoglobin are contributed by the lens epithelium and apolipoproteins and fibrinogen by the aqueous humor to the PEX material. Pathway analysis of the identified novel protein constituents and genes or proteins previously implicated in the disease reiterated the involvement of extracellular matrix organization and degradation, elastic fiber formation, and complement cascade in PEX syndrome. Network analysis suggested a central role of fibronectin in the pathophysiology of the disease. The identified novel protein constituents of PEX material also shed light on the molecular basis of the association of PEX syndrome with heart disease, stroke, and Alzheimer disease. This study expands the understanding of the protein composition of pathological PEX material deposited on the ocular lens in patients with PEX syndrome and provides useful insights into the pathophysiology of this disease. This study together with the previous study by our group (Sharma et al. Experimental Eye Research 2009;89(4):479-85) demonstrate that using neat PEX material, devoid of the underlying lens capsule, for proteomics analysis is an effective approach for deciphering the protein composition of complex and highly insoluble extracellular pathological ocular deposits present in patients with PEX syndrome. Show less

An accumulation of data from in vitro to in vivo model system has established a pivotal role of three crucial ligand activated nuclear receptors RXR, LXR-alpha and VDR for their ability to regulate an array of genes involved in regulation of fundamental cellular processes to patho-physiological situations. Keeping in view RXR as a common heterodimeric partner for LXR-alpha and VDR, the present study was designed to dissect the interrelationship between these three nuclear receptors in peripheral blood mononuclear cellular model. The present study revealed that all the three nuclear receptors displayed auto regulation in response to their specific ligands; Both LXR-alpha and VDR regulated the expression of their heterodimeric partner RXR; and VDR was regulated by LXR-alpha through its ability to modulate SREBP response element present in the promoter region of VDR gene. Based on these findings, the role of these nuclear receptors could be better understood in various nuclear receptor mediated pathological processes. Show less

Recent studies on the liver X receptor-alpha (LXR-alpha) have recognized its crucial protective role in the initiation of a cross-talk between lipid metabolism and inflammation regarded as a prerequisite for the development of atherosclerotic lesions. The present study was directed to explore the functional genomics of LXR-alpha gene within blood mononuclear cells of subjects suffering from coronary heart disease (CHD), revealed a paradoxical relationship between blood cellular LXR-alpha mRNA expression and the severity of coronary occlusion. In order to resolve this apparent paradox, the ligand binding domain of LXR-alpha gene was analyzed. The results of such a study revealed that three critical mutations in the domain comprising of amino acids Asp324, Pro327 and Arg328, were responsible for inability of this domain to interact with its natural ligands leading thereby to deregulation of its effector genes that are known to play crucial role in the cross-talk between lipid peroxidation and inflammation. This phenomenon was in conformity with functional assay of LXR-alpha dependent transcriptional activity within cells derived from normal and CHD subjects. Based upon these results we propose that the mutations in the LXR-alpha gene reported here for the first time not only may be exploited for the diagnosis of CHD in human subjects but also could be used as a marker for exploring the predisposition of human subjects towards CHD. Show less