ABSTRACT
Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for in public metabolomics datasets to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans, including N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids. Using repository-scale analysis1,2, we discovered that some conjugated bile acids are associated with inflammatory bowel disease (IBD). Validation using four distinct human IBD cohorts showed that cholic acids conjugated to Glu, Ile/Leu, Phe, Thr, Trp or Tyr are increased in Crohn's disease. Several of these compounds and related structures affected pathways associated with IBD, such as interferon-γ production in CD4+ T cells3 and agonism of the pregnane X receptor4. Culture of bacteria belonging to the Bifidobacterium, Clostridium and Enterococcus genera produced these bile amidates. Because searching repositories with tandem mass spectrometry spectra has only recently become possible, this reverse metabolomics approach can now be used as a general strategy to discover other molecules from human and animal ecosystems.
Subject(s)
Amides , Bile Acids and Salts , Esters , Fatty Acids , Metabolomics , Animals , Humans , Bifidobacterium/metabolism , Bile Acids and Salts/chemistry , Bile Acids and Salts/metabolism , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Clostridium/metabolism , Cohort Studies , Crohn Disease/metabolism , Enterococcus/metabolism , Esters/chemistry , Esters/metabolism , Fatty Acids/chemistry , Fatty Acids/metabolism , Inflammatory Bowel Diseases/metabolism , Metabolomics/methods , Phenotype , Pregnane X Receptor/metabolism , Reproducibility of Results , Tandem Mass Spectrometry , Amides/chemistry , Amides/metabolismABSTRACT
Physical therapy (PT) has been shown to be a helpful intervention in the treatment of chemotherapy-induced peripheral neuropathy (CIPN). Our aim was to screen for CIPN in patients with hematologic malignancies receiving vincristine chemotherapy and obtain a baseline assessment on the percentage of patients utilizing PT in the treatment of CIPN. A retrospective review of surveys administered to parents and patients regarding the severity of peripheral neuropathy symptoms from October 2016 through March 2018 was conducted. Of 116 patients, a total of 102 patients (67 male and 35 female; 4 to 10 y of age, N=63; 11 to 15 y of age, N=19; 16 to 20 y of age, N=20) were eligible for the study, with 67.6% (N=69) reporting symptoms of CIPN. Of these patients, 16.7% scored 4 or greater on the surveys, suggesting clinically severe CIPN. Common parental concerns included decreased strength, difficulty walking up stairs, tripping, and foot drops. Approximately 55.1% of the 69 patients who reported CIPN symptoms were referred to outpatient PT, while 44.9% were not referred. A simple survey consisting of 4 questions that only took several minutes to administer was capable of identifying CIPN in 67.6% of patients receiving vincristine chemotherapy.
Subject(s)
Antineoplastic Agents , Hematologic Neoplasms , Peripheral Nervous System Diseases , Adult , Antineoplastic Agents/adverse effects , Child , Female , Hematologic Neoplasms/drug therapy , Humans , Male , Middle Aged , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/diagnosis , Physical Therapy Modalities , Quality of Life , Vincristine/adverse effects , Young AdultABSTRACT
Objective We compared an infrared temporal artery thermometer with our clinical standard axillary thermometer for temperature measurements in neonatal patients. Study Design We measured temporal artery (Tta), axillary (Tax, clinical standard), and rectal (Tr, gold standard) temperatures of 49 infants. The difference between Tr and Tta was compared with that between Tr and Tax, and the data were analyzed based on bed type and postmenstrual age. Results The mean Tta, Tax, and Tr were 37.16 (SD 0.36) °C, 36.61 (SD 0.30) °C, and 36.82 (SD 0.30) °C, respectively. The measurements by these methods were all significantly different. The mean Tr-Tax was 0.21 (SD 0.26) °C, and the mean Tr-Tta was -0.34 (SD 0.37) °C, indicating that Tax was closer to Tr than was Tta (p < 0.0001). Tta agreed more closely with Tr for infants in cribs than for those in incubators. Adjusting for bed type and body weight, with each week of postmenstrual age, the discrepancy between Tr-Tta and Tr-Tax decreased by 0.005°C (p = 0.034). Conclusion Compared with the gold standard, Tr, Tta is not more accurate than Tax. The temporal artery thermometer was less accurate for infants in incubators than for infants in cribs. The accuracy of temporal artery temperature increased with postmenstrual age.
Subject(s)
Body Temperature , Temporal Arteries , Thermometry/methods , Axilla , Female , Humans , Incubators, Infant , Infant Equipment , Infant, Newborn , Male , Rectum , Thermometers , Thermometry/instrumentationABSTRACT
We conducted a quality improvement project from 2019 to 2021 at a single home health agency to reduce rates of central line-associated bloodstream infection in our ambulatory pediatric population. Annualized central line-associated bloodstream infection rates per 1,000 catheter line days decreased by 20 % during the study period, from a rate of 1.023 to 0.810. This decrease was sustained in the 10-month post-study period with a center line shift of 1.090 to 0.658.