Proteomic changes upon treatment with semaglutide in individuals with obesity.

Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways.

Single-Cell Advances in Investigating and Understanding Chronic Kidney Disease and Diabetic Kidney Disease.

Chronic kidney disease (CKD) and its subset diabetic kidney disease are progressive conditions that affect >850 million people worldwide. Diabetes, hypertension, and glomerulonephritis are the most common causes of CKD, which is associated with significant patient morbidity and an increased risk of cardiovascular events, such as heart failure, ultimately leading to premature death. Despite newly approved drugs, increasing evidence shows that patients respond to treatment differently given the complexity of disease heterogeneity and complicated pathophysiology.

When the Psychiatrist Morally Disapproves.

The understanding of concepts like moral distress and countertransference in mental health settings has advanced over time. While organizational constraints and the clinician's moral values are conventionally thought to play a part in evoking such responses, certain behavioral transgressions might be universally deemed as morally unacceptable. The authors present case scenarios that took place during forensic assessments and routine clinical care.

pyTFA and matTFA: a Python package and a Matlab toolbox for Thermodynamics-based Flux Analysis.

Summary: pyTFA and matTFA are the first published implementations of the original TFA paper. Specifically, they include explicit formulation of Gibbs energies and metabolite concentrations, which enables straightforward integration of metabolite concentration measurements.

Motivation: High-throughput analytic technologies provide a wealth of omics data that can be used to perform thorough analyses for a multitude of studies in the areas of Systems Biology and Biotechnology.

A design-build-test cycle using modeling and experiments reveals interdependencies between upper glycolysis and xylose uptake in recombinant and improves predictive capabilities of large-scale kinetic models.

Background: Recent advancements in omics measurement technologies have led to an ever-increasing amount of available experimental data that necessitate systems-oriented methodologies for efficient and systematic integration of data into consistent large-scale kinetic models. These models can help us to uncover new insights into cellular physiology and also to assist in the rational design of bioreactor or fermentation processes. Optimization and Risk Analysis of Complex Living Entities (ORACLE) framework for the construction of large-scale kinetic models can be used as guidance for formulating alternative metabolic engineering strategies.

Reconstruction of biological pathways and metabolic networks from in silico labeled metabolites.

Reaction atom mappings track the positional changes of all of the atoms between the substrates and the products as they undergo the biochemical transformation. However, information on atom transitions in the context of metabolic pathways is not widely available in the literature. The understanding of metabolic pathways at the atomic level is of great importance as it can deconvolute the overlapping catabolic/anabolic pathways resulting in the observed metabolic phenotype.

Identification of metabolic engineering targets for the enhancement of 1,4-butanediol production in recombinant E. coli using large-scale kinetic models.

Rational metabolic engineering methods are increasingly employed in designing the commercially viable processes for the production of chemicals relevant to pharmaceutical, biotechnology, and food and beverage industries. With the growing availability of omics data and of methodologies capable to integrate the available data into models, mathematical modeling and computational analysis are becoming important in designing recombinant cellular organisms and optimizing cell performance with respect to desired criteria. In this contribution, we used the computational framework ORACLE (Optimization and Risk Analysis of Complex Living Entities) to analyze the physiology of recombinant Escherichia coli producing 1,4-butanediol (BDO) and to identify potential strategies for improved production of BDO.

Constraining the flux space using thermodynamics and integration of metabolomics data.

Flux balance analysis of stoichiometric metabolic models has become one of the most common methods for estimating intracellular fluxes. However most of these networks are underdetermined and can have multiple alternate optimal flux distributions. Thermodynamic constraints can reduce the solution space significantly and at the same time provide a platform for the integration of metabolomics data.

Towards kinetic modeling of genome-scale metabolic networks without sacrificing stoichiometric, thermodynamic and physiological constraints.

Mathematical modeling is an essential tool for the comprehensive understanding of cell metabolism and its interactions with the environmental and process conditions. Recent developments in the construction and analysis of stoichiometric models made it possible to define limits on steady-state metabolic behavior using flux balance analysis. However, detailed information on enzyme kinetics and enzyme regulation is needed to formulate kinetic models that can accurately capture the dynamic metabolic responses.

Colonic architectural change on colonoscopy in patients taking psychotropic medications.

Background: Patients on psychotropic medications have been clinically observed to have higher rates of abnormal colonic architecture resulting in difficult colonoscopies. This study aims to determine if a correlation between use of psychotropic medications and colonic architectural change seen on colonoscopy exists.

Methods: A retrospective case-control study was undertaken with 252 adults selected from the hospital endoscopy database between January 2006 and July 2008.

From network models to network responses: integration of thermodynamic and kinetic properties of yeast genome-scale metabolic networks.

Many important problems in cell biology arise from the dense nonlinear interactions between functional modules. The importance of mathematical modelling and computer simulation in understanding cellular processes is now indisputable and widely appreciated. Genome-scale metabolic models have gained much popularity and utility in helping us to understand and test hypotheses about these complex networks.

DREAMS of metabolism.

Metabolic networks have been studied for several decades, and sophisticated computational frameworks are needed to augment experimental approaches to harness these complex networks. BNICE (Biochemical Network Integrated Computational Explorer), a computational approach for the discovery of novel biochemical pathways that is based on biochemical transformations, overcomes many of the current limitations. BNICE and similar frameworks can be used in several different areas: (i) 'Design' of novel pathways for metabolic engineering; (ii) 'Retrosynthesis' of metabolic compounds; (iii) 'Evolution' analysis between metabolic pathways of different organisms; (iv) 'Analysis' of metabolic pathways; (v) 'Mining' of omics data; and (vi) 'Selection' of targets for enzyme engineering.

Network thermodynamics in the post-genomic era.

Network models have been used to study the underlying processes and principles of biological systems for decades, providing many insights into the complexity of life. Biological systems require a constant flow of free energy to drive these processes that operate away from thermodynamic equilibrium. With the advent of high-throughput omics technologies, more and more thermodynamic knowledge about the biological components, processes and their interactions are surfacing that we can integrate using large-scale biological network models.

Panic attack and its correlation with acute coronary syndrome - more than just a diagnosis of exclusion.

The panic attack is able to mimic the clinical presentation of an acute coronary syndrome (ACS), to the point of being clinically indistinguishable without appropriate investigations. However, the literature actually demonstrates that the 2 conditions are more related than just being differential diagnoses. Through a review of the literature involving epidemiological studies, randomised controlled trials, systematic reviews and meta-analyses found on a Medline search, the relation between panic disorder and ACS is explored in greater depth.

Somatic and non-affective symptoms of old age depression: ethnic differences among Chinese, Indians and Malays.

Background: Somatic and other non-affective symptomatology characterizes late life depression and contributes to its under-diagnosis, especially in some ethnic groups.

Objectives: We examined variations in non-affective presentation and its health and functional significance across different ethnic groups of Chinese, Malays and Indians.

Method: We analyzed data from the National Mental Health Survey for Elderly, a population-based cross-sectional study of older adults aged 60 and above (N = 1092).

Is the routine check nephrostogram following percutaneous antegrade ureteric stent placement necessary?

Our aim was to review our experience with percutaneous antegrade ureteric stent (PAUS) placement and to determine if the routinely conducted check nephrostogram on the day following ureteric stent placement was necessary. Retrospective review of patients who had undergone PAUS placement between January 2004 and December 2005 was performed. There were 83 subjects (36 males, 47 females), with a mean age of 59.