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Biomedical subjects

Rishi Jain

Publications and source records attributed to Rishi Jain.

6 recordsLinked to original sources

Associations between prescribed amphetamines and spontaneous cervical artery dissection: a matched case-control study.

AIMS: To assess whether prescribed amphetamines are associated with spontaneous cervical artery dissection (sCeAD), an important cause of stroke in young adults. METHODS: We conducted a retrospective matched case-control study within a large academic health system in Chicago, Illinois. Adults aged 18-85 years with incident sCeAD were matched 1:4 to controls without dissection on age, sex, and race/ethnicity. The primary exposure was documented amphetamine prescription. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) controlling for relevant vascular and clinical covariates. Sensitivity analyses included strict matched-strata and inverse probability-weighted models. RESULTS: Among 11,463 individuals, including 2,293 cases and 9,170 controls, amphetamine exposure was associated with higher odds of sCeAD (adjusted OR 1.70, 95% CI 1.18-2.46). Results were unchanged in strictly matched strata (OR 1.70, 95% CI 1.18-2.46) and remained directionally consistent after inverse probability weighting (OR 1.40, 95% CI 1.09-1.79). High-dose amphetamine exposure (≥30 mg/day) had the strongest association (OR 1.96, 95% CI 1.18-3.26), whereas low-dose exposure was not statistically significant. CONCLUSION: Prescribed amphetamines were associated with modestly increased odds of sCeAD. While these findings are observational and hypothesis-generating, they may support a possible association in susceptible patients.

Humans↗

Bayesian-based selection of metabolic objective functions.

MOTIVATION: A critical component of in silico analysis of underdetermined metabolic systems is the identification of the appropriate objective function. A common assumption is that the objective of the cell is to maximize growth. This objective function has been shown to be consistent in a few limited experimental cases, but may not be universally appropriate. Here a method is presented to quantitatively determine the most probable objective function. RESULTS: The genome-scale metabolism of Escherichia coli growing on succinate was used as a case-study for analysis. Five different objective functions, including maximization of growth rate, were chosen based on biological plausibility. A combination of flux balance analysis and linear programming was used to simulate cellular metabolism, which was then compared to independent experimental data using a Bayesian objective function discrimination technique. After comparing rates of oxygen uptake and acetate production, minimization of the production rate of redox potential was determined to be the most probable objective function. Given the appropriate reaction network and experimental data, the discrimination technique can be applied to any bacterium to test a variety of different possible objective functions. SUPPLEMENTARY INFORMATION: Additional files, code and a program for carrying out model discrimination are available at http://www.engr.uconn.edu/~srivasta/modisc.html.

Algorithms↗

Structure-activity studies on a library of potent calix[4]arene-based PDGF antagonists that inhibit PDGF-stimulated PDGFR tyrosine phosphorylation.

Platelet-derived growth factor (PDGF) and its receptor PDGFR are required for tumor growth and angiogenesis, so disruption of the PDGF-PDGFR interaction should lead to starvation of tumors and reduction of tumor growth. Potent PDGF antagonists have been discovered through the synthesis of a series of calix[4]arene-based compounds that are designed to bind to the three-loop region of PDGF. The effect of lower-rim alkylation, linker and number of interacting head groups on the calix[4]arene scaffold on PDGF affinity and cellular activity has been investigated.

Amino Acid Sequence↗

Protein recognition using synthetic surface-targeted agents.

The design of synthetic agents to disrupt protein-protein interactions has received relatively little attention in recent years. In this review we describe strategies for targeting different types of protein surfaces using mimetics of protein secondary or tertiary structure. In this way strong and selective binding to a protein surface has be achieved and disruption of clinically important protein-protein interactions has been demonstrated in models of human disease.

Amino Acid Sequence↗

Role of repeat fine-needle aspiration biopsy (FNAB) in the management of thyroid nodules.

The purpose of the present study was to determine the role of repeat fine-needle aspiration biopsy (FNAB) in the evaluation of thyroid nodules initially classified as "nondiagnostic" due to limited cellularity or as "indeterminate for neoplasm." We reviewed a cohort of 431 patients (352 females, 79 males; average age 50 yr); 237 patients were classified as "nondiagnostic" due to limited cellularity and 194 as "indeterminate for neoplasm" over a 3-yr period (1999-2002). Repeat FNAB under ultrasound guidance was performed in 226 patients (226/431, 52%); surgical pathology results were available in 101 patients. Repeat FNAB diagnoses were: benign 70 (31%), follicular/Hürthle cell neoplasm 62 (27%), suspicious for papillary carcinoma 25 (12%), malignant 17 (7%), and nondiagnostic 52 (23%) cases. Surgical follow-up was available in 101 (45%) patients; malignancy was identified in 50 (49%) patients. The malignancy rate was 51% and 48% in cases in which initial FNAB was nondiagnostic and indeterminate for neoplasm, respectively. There were no false-positives and all malignant cases undergoing surgery were found to be malignant. This study demonstrates that repeat FNAB is warranted in patients with thyroid nodules diagnosed on initial FNAB as nondiagnostic and indeterminate for neoplasm since it can yield a definitive diagnosis in the majority of cases with an overall malignancy rate of 49%.

Adenoma, Oxyphilic↗

Investigation of bacteriophage MS2 viral dynamics using model discrimination analysis and the implications for phage therapy.

Lytic phages infect their bacterial hosts, use the host machinery to replicate, and finally lyse and kill their hosts, releasing progeny phages. Various mathematical models have been developed that describe these phage-host viral dynamics. The aim of this study was to determine which of these models best describes the viral dynamics of lytic RNA phage MS2 and its host Escherichia coli C-3000. Experimental data consisted of uninfected and infected bacterial cell densities, free phage density, and substrate concentration. Parameters of various models were either determined directly through other experimental techniques or estimated using regression analysis of the experimental data. The models were evaluated using a Bayesian-based model discrimination technique. Through model discrimination it was shown that phage-resistant cells inhibited the growth of phage population. It was also shown that the uninfected bacterial population was a quasispecies consisting of phage-sensitive and phage-resistant bacterial cells. When there was a phage attack the phage-sensitive cells died out and the phage-resistant cells were selected for and became the dominant strain of the bacterial population.

Cell Proliferation↗