Evaluation of multiple variate selection methods from a biological perspective: a nutrigenomics case study

Genomics-based technologies produce large amounts of data. To interpret the results and identify the most important variates related to phenotypes of interest, various multivariate regression and variate selection methods are used. Although inspected for statistical performance, the relevance of multivariate models in interpreting biological data sets often remains elusive. We compare various multivariate regression and variate selection methods applied to a nutrigenomics data set in terms of performance, utility and biological interpretability. The studied data set comprised hepatic transcriptome (10,072 predictor variates) and plasma protein concentrations [2 dependent variates: Leptin (LEP) and Tissue inhibitor of metalloproteinase 1 (TIMP-1)] collected during a high-fat diet study in ApoE3Leiden mice. The multivariate regression methods used were: partial least squares “PLS”; a genetic algorithm-based multiple linear regression, “GA-MLR”; two least-angle shrinkage methods, “LASSO” and “ELASTIC NET”; and a variant of PLS that uses covariance-based variate selection, “CovProc.” Two methods of ranking the genes for Gene Set Enrichment Analysis (GSEA) were also investigated: either by their correlation with the protein data or by the stability of the PLS regression coefficients. The regression methods performed similarly, with CovProc and GA performing the best and worst, respectively (R-squared values based on “double cross-validation” predictions of 0.762 and 0.451 for LEP; and 0.701 and 0.482 for TIMP-1). CovProc, LASSO and ELASTIC NET all produced parsimonious regression models and consistently identified small subsets of variates, with high commonality between the methods. Comparison of the gene ranking approaches found a high degree of agreement, with PLS-based ranking finding fewer significant gene sets. We recommend the use of CovProc for variate selection, in tandem with univariate methods, and the use of correlation-based ranking for GSEA-like pathway analysis methods

Telerehabilitation of a Patient Post-buttockectomy and Internal Hemipelvectomy Secondary to Pelvic Round Cell Sarcoma during the COVID-19 Pandemic: A Case Report

Pelvic sarcomas are rare malignancies that can result in extensive surgeries involving bone and soft tissue resection, which can greatly improve with rehabilitation. However, due to the restrictions brought about by the COVID-19 pandemic, the rehabilitation of patients with pelvic sarcomas was affected. Limited information is also presented in the literature regarding the rehabilitation of patients with lower extremity surgeries undergoing telerehabilitation and during a pandemic. This study presents the rehabilitation process of a 43-year-old woman diagnosed with pelvic round cell sarcoma of the right gluteal area during the COVID-19 pandemic. The patient underwent wide excision, buttockectomy and internal hemipelvectomy, and we measured outcomes using the Tinetti assessment tool (TAT) and Lower Extremity Functional Scale (LEFS). A decreased risk of falls and improved functional performance were recorded using the TAT and LEFS respectively. Telerehabilitation was noted to have a good satisfaction rate among the patient and health workers.&#x0D; Telerehabilitation may be an effective alternative to face-to-face therapy during the COVID-19 pandemic. More studies are needed to look into the conduct of telerehabilitation intervention among patients with bone and soft tissue surgeries.</jats:p

Factors associated with self-care behavior among heart failure patients in India: A systematic review

Self-care is crucial for heart failure management and complements pharmacological treatments; however, various factors hinder effective self-care, adversely affecting clinical outcomes and leading to poor quality of life. This systematic review aimed to identify factors influencing self-care behaviors among heart failure patients in India. The search was conducted in six databases, PubMed, CINAHL, Scopus, ProQuest, Web of Science, and Embase; between January 2012 and September 2024, 676 articles were reviewed. After removing duplicates, seven articles were included for analysis on the basis of the study inclusion criteria. The PRISMA guidelines has been used in this review. We included observational, cross-sectional, experimental, quasiexperimental, and qualitative studies published in English and conducted in India. The included studies were critically appraised using the Joanna Briggs Institute’s risk of bias tool. The data were synthesized narratively. The findings revealed various factors that influence self-care behavior, which were divided into favorable and hindering factors. The factors that favored self-care behavior were self-efficacy, disease-related knowledge, situational awareness, adequate family income, financial support, health insurance, supportive family, patient willpower, and confidence in healthcare. However, low education, lack of knowledge about heart failure, difficulty understanding health information, limited time spent by healthcare providers, low health literacy, low self-efficacy, financial difficulties, negative emotions, and lack of structured care plans hindered self-care. These findings underscore the need for health policies that prioritize patient education, accessible care and adequate financial support. Strengthening such policies could improve self-care adherence among heart failure patients, enhancing clinical outcomes and quality of life

Chronic kidney disease and its relationship with intake of turmeric, catechins, proanthocyanidins and omega-3

Publisher Copyright: © 2015, Grupo Aula Medica S.A. All Rights Reserved.Chronic renal disease is characterized by decreased glomerular filtration rate (GFR) < 60 ml/min/ 1.73m2 and/or the presence of kidney damage independent of the cause for a period of 3 months or more. The treatment of more advanced stages of chronic kidney disease is dialysis, and most common form of hemodialysis. This treatment is costly in our country reaching USD 900 per person. The main cause of admission to dialysis, diabetic nephropathy remains with 34% of all revenue. This alone makes any improvement in the treatment of CKD is highly desirable. There is evidence available about the fundamental role of turmeric, proanthocyanidins, catechins and omega-3 on how these compounds are related to the response to treatment of chronic kidney disease for various reasons

An alternate binding site for PPARγ ligands

PPARγ is a target for insulin sensitizing drugs such as glitazones, which improve plasma glucose maintenance in patients with diabetes. Synthetic ligands have been designed to mimic endogenous ligand binding to a canonical ligand-binding pocket to hyperactivate PPARγ. Here we reveal that synthetic PPARγ ligands also bind to an alternate site, leading to unique receptor conformational changes that impact coregulator binding, transactivation and target gene expression. Using structure-function studies we show that alternate site binding occurs at pharmacologically relevant ligand concentrations, and is neither blocked by covalently bound synthetic antagonists nor by endogenous ligands indicating non-overlapping binding with the canonical pocket. Alternate site binding likely contributes to PPARγ hyperactivation in vivo, perhaps explaining why PPARγ full and partial or weak agonists display similar adverse effects. These findings expand our understanding of PPARγ activation by ligands and suggest that allosteric modulators could be designed to fine tune PPARγ activity without competing with endogenous ligands

Defining a canonical ligand-binding pocket in the orphan nuclear receptor Nurr1

Nuclear receptor related 1 protein (Nurr1/NR4A2) is an orphan nuclear receptor that is considered to function without a canonical ligand-binding pocket. A crystal structure of the Nurr1 ligand-binding domain (LBD) revealed no physical space in the conserved region where other nuclear receptors with solvent accessible apo-protein ligand-binding pockets bind synthetic and natural ligands. Using solution NMR spectroscopy, hydrogen/deuterium exchange mass spectrometry, and molecular dynamics simulations, we show here that the putative canonical ligand-binding pocket in the Nurr1 LBD is dynamic with high solvent accessibility, exchanges between two or more conformations on the microsecond-to-millisecond timescale, and can expand from the collapsed crystalized conformation to allow binding of unsaturated fatty acids. These findings should stimulate future studies to probe the ligandability and druggability of Nurr1 for both endogenous and synthetic ligands, which could lead to new therapeutics for Nurr1-related diseases, including Parkinson’s disease and schizophrenia.</jats:p