Chemical isotope labeling liquid chromatography mass spectrometry for investigating acute dietary effects of cow milk consumption on human urine metabolome

Biomarker discovery has been increasingly important in the field of metabolomics for the detection and understanding of diseases. Of the many biofluids available for metabolomics, urine is a preferred option as it is non-invasive to collect and contains a wide range of metabolites reflective of the health status of the testing individual. However, urine also contains many exogenous metabolites which are introduced through various sources such as diet. This complicates the data interpretation when searching the metabolome for disease-related endogenous metabolites. Since diet is difficult to control, this work aims to study the acute effects of diet (particularly cow milk) consumption on the human urine amine/phenol submetabolome by utilizing differential chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS). LC-MS analysis of 62 urine samples collected before and after (1 hour and 2 hours) milk intake resulted in the detection of 4985 metabolites with an average of 3815 ± 206 (n = 62) detected per sample. The work aims to differentiate the exogenous “food” metabolites from the endogenous metabolite pool and to determine any dietary effects from milk intake on the human urine metabolome.     

Chronic inflammation and risk of lung cancer in older adults in the health,aging and body composition cohort study

Objectives

We examined the association between three inflammatory markers (Interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) and incident lung cancer using baseline, updated, and averaged inflammatory measures in older adults.

The efficacy of DNA mixture to mixture matching

Standard practice in forensic science is to compare a person of interest’s (POI) reference DNA profile with an evidence DNA profile and calculate a likelihood ratio that considers propositions including and excluding the POI as a DNA donor. A method has recently been published that provides the ability to compare two evidence profiles (of any number of contributors and of any level of resolution) comparing propositions that consider the profiles either have a common contributor, or do not have any common contributors. Using this method, forensic analysts can provide intelligence to law enforcement by linking crime scenes when no suspects may be available. The method could also be used as a quality assurance measure to identify potential sample to sample contamination. In this work we analyse a number of constructed mixtures, ranging from two to five contributors, and with known numbers of common contributors, in order to investigate the performance of using likelihood ratios for mixture to mixture comparisons. Our findings demonstrate the ability to identify common donors in DNA mixtures with the power of discrimination depending largely on the least informative mixture of the pair being considered. The ability to match mixtures to mixtures may provide intelligence information to investigators by identifying possible links between cases which otherwise may not have been considered connected.     

Bypass Surgery or Stenting for Left Main Coronary Artery Disease in Patients With Diabetes

Background

The randomized EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial reported a similar rate of the 3-year composite primary endpoint of death, myocardial infarction (MI), or stroke in patients with left main coronary artery disease (LMCAD) and site-assessed low or intermediate SYNTAX scores treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Whether these results are consistent in high-risk patients with diabetes, who have fared relatively better with CABG in most prior trials, is unknown.

Heterogeneous effects of obesity on mental health: Evidence from Mexico

Obesity can spread more easily if it is not perceived negatively. This issue may be more pronounced among the poor, a conjecture that we test in this paper. We start with general evidence on the concave relationship between income and obesity, both across countries and within Mexico, a country characterized by very unequal development levels and the highest obesity rate in the world. We suggest a general model that explains this stylized fact from a simple necessary condition, namely, the complementarity between nonfood consumption and health concerns. Then, we test the direct effect of overweight on mental health among Mexican women. We find a positive effect of obesity in the low consumption group and a depressing effect among the rich. This result is robust to the inclusion of a range of confounders (childhood conditions, lifestyle variables, food expenditure, and household shocks) and after instrumenting individual fatness by the variation in genetic predisposition. The complementarity between living standards and weight concerns may reflect different norms, different labor market penalties, or simply different returns to healthy time across the social spectrum.     

Colitis following the use of immune checkpoint inhibitors: A real-world analysis of spontaneous reports submitted to the FDA adverse event reporting system

BackgroundAlthough colitis has been reported in patients treated with immune checkpoint inhibitors (ICIs), associations between colitis and ICIs had not been thoroughly assessed in real-world studies. Here, we identified and characterized significant colitis-associated with ICIs.MethodsBased on the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2019, the disproportionality analysis and Bayesian analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were adopted to data mining of the suspected adverse events of colitis after ICIs administrating. Clinical characteristics of patients with ICIs-associated colitis and the time to onset of colitis following different ICI regimens were collected.ResultsA total of 3786 reports of colitis adverse events were identified with ICIs. Seven ICI monotherapies were associated with the reporting of colitis. Statistically significant ROR, PRR, information component (IC), and empirical Bayesian geometric mean (EBGM) emerged for all ICI monotherapies and combination therapies. ICIs-associated colitis affected mostly male (53.51%), with a wide mean age range (60.65 to 72 years). Colitis adverse events were commonly reported in patients with melanoma and lung cancer. Adverse outcomes of colitis concerning ICI were mainly outcomes of hospitalization-initiated or prolonged and other serious. Among colitis cases, 17.43% cases of colitis concerning ICI lead to death. The adverse event of colitis occurred earliest in ipilimumab monotherapy with a median time to onset of 64.21 days (IQR: 27–69 days) among all monotherapies.ConclusionsICI may lead to severe and disabling ICIs-associated colitis during therapy. Analysis of FAERS data identified signals for adverse events of colitis with ICI regimens. Practitioners should consider the factors that may increase the likelihood of colitis. The findings support a continued surveillance and risk factor identification studies.     

Colon Cancer in Patients Under 25 Years Old: A Different Disease?

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Thirty-Day Morbidity after Simultaneous Resection of Colorectal Cancer and Colorectal Liver Metastasis: American College of Surgeons NSQIP Analysis

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