Search

Understanding exercise metabolism and the relationship with volatile organic compounds (VOCs) holds potential in both health care and sports performance. Exercise metabolism can be investigated using whole body exercise testing (in vivo) or through the culture and subsequent electrical pulse stimulation (EPS) of myotubes (in vitro). This research investigates the novel headspace (HS) analysis of EPS skeletal muscle myotubes. An in vitro system was built to investigate the effect of EPS on the volatile constituents in the HS above EPS skeletal muscle. The C2C12 immortalised cell line was chosen. EPS was applied to the system to induce myotube contraction. The in vitro system was applied to the analysis of VOCs using thermal desorption (TD) sampling. Samples were collected under four conditions: environmental samples (enviro), acellular media HS samples (blank), skeletal muscle myotubes without stimulation HS samples (baseline) and EPS of skeletal muscle myotube HS samples (stim). TD sampling combined with gas-chromatography mass spectrometry (GC-MS) detected two compounds that, after multivariate and univariate statistical analysis, were identified as changing due to EPS (p < 0.05). These compounds were tentatively assigned as 1,4-Dioxane-2,5-dione, 3,6-dimethyl- and 1-pentene. The former is a known lactide and the latter has been reported as a marker of oxidative stress. Further research should focus on improvements to the EPS system, including the use of more relevant cell lines, quantification of myotube contractions, and the application of targeted analysis, metabolic assays and media analysis.

The identification and recovery of suspected human biofluid evidence can present a bottleneck in the crime scene investigation workflow. Crime Scene Investigators typically deploy one of a number of presumptive enhancement reagents, depending on what they perceive an analyte to be; the selection of this reagent is largely based on the context of suspected evidence and their professional experience. Positively identified samples are then recovered to a forensic laboratory where confirmatory testing is carried out by large lab-based instruments, such as through mass-spectrometry-based techniques. This work proposes a proof-of-concept study into the use of a small, robust and portable ion mobility spectrometry device that can analyse samples in situ, detecting, identifying and discriminating commonly encountered body fluids from interferences. This analysis exploits the detection and identification of characteristic volatile organic compounds generated by gentle heating, at ambient temperature and pressure, and categorises samples using machine learning, providing investigators with instant identification. The device is shown to be capable of producing characteristic mobility spectra using a dual micro disc pump configuration which separates blood and urine from three visually similar interferences using an unsupervised PCA model with no misclassified samples. The device has the potential to reduce the need for potentially contaminating and destructive presumptive tests, and address the bottleneck created by the time-consuming and laborious detection, recovery and analysis workflow currently employed.

Abstract Background Fatty acids, specifically polyunsaturated fatty acids (PUFAs) play an important role in inflammation and its resolution, however, their interaction with the epigenome is relatively unexplored. Here we investigate the relationship between circulating blood fatty acids and the DNA methylation of the cytokine encoding gene tumour necrosis factor (TNF, OMIM 191160). Methods Using a cross‐sectional study approach, we collected blood samples from adults (N=88 (30 males, 58 females); 18–74 years old) for DNA methylation pyrosequencing analysis at four sites in TNF exon 1 and gas‐chromatography mass‐spectrometry analysis of the fatty acid profile of dried blood spots (DBS). Results Methylation levels of TNF exon 1 are significantly correlated with specific fatty acids in a gender‐specific manner. In the males the PUFAs Docosahexaenoic Acid (DHA) and Arachidonic Acid (AA) were positively associated with TNF methylation, as was the saturated fatty acid (SFA) Stearic Acid; in contrast, mono‐unsaturated fatty acids (MUFAs) had a negative association. In the females, omega‐6 PUFA γ‐Linolenic acid (GLA) was negatively correlated with TNF methylation; Adrenic acid and Eicosadienoic Acid were positively correlated with TNF methylation. Conclusion These results suggest that one way that fatty acids interact with the inflammation is through altered methylation profiles of cytokine genes; thus, providing potential therapeutic targets for nutritional and health interventions.

Interpersonal psychotherapy (IPT) prevents weight gain and reduces loss-of-control (LOC)-eating in adults. However, IPT was not superior to health-education (HE) for preventing excess weight gain and reducing LOC-eating over 1-year in adolescent girls at risk for excess weight gain and eating disorders. Limited data suggest that older and non-White youth may be especially responsive to IPT. In secondary analyses, we examined if age or race moderated weight and LOC-eating outcomes. The 113 participants (12–17 years; 56.6% White) from the original trial were re-contacted 3 years later for assessment. At baseline and follow-up visits through 3 years, we assessed BMI, adiposity by dual energy X-ray absorptiometry, and LOC-eating presence. In linear mixed models, baseline age moderated 3-year BMI outcome; older girls in IPT had the lowest 3-year BMI gain compared to younger girls in IPT and all girls in HE, p = 0.04. A similar pattern was observed for adiposity. Race moderated 3-year LOC-eating; non-White girls in IPT were most likely to abstain from LOC-eating at 3 years compared to all other girls, p = 0.04. This hypothesis-generating analysis suggests future studies should determine if IPT is especially efficacious at reducing LOC-eating in older, non-White adolescents.

Background. The prevalence of fecal incontinence varies tremendously as a result of inadequate data collection methods. Few office-based studies have assessed the prevalence of fecal incontinence and none have looked at modifiable risk factors or effect on quality of life. Design, Settings, Patients, and Main Outcome Measures. Five hundred patients who visited our inner city, university-based gastroenterology practice, were asked about symptoms of fecal incontinence. We also retrospectively reviewed 500 charts to identify the frequency of patient-physician reporting of fecal incontinence. Results. Of the 500 patients that were directly questioned, 58 (12%, 43 women, 15 men) admitted to fecal incontinence compared to 12 (2.4%) in the retrospective arm. Patients with fecal incontinence and loose/watery stool reported the lowest quality of life scores. While the average severity score was similar between men and women, women had a significantly lower average quality of life score (3.04 versus 2.51; P

UPLC-ion mobility spectrometry separations combined with mass spectrometry (UPLC-IM-MS) and tandem mass spectrometry (UPLC-IM-MS/MS) have been investigated for the simultaneous determination of testosterone and epitestosterone glucuronides in urine. The glucuronide epimers of testosterone and epitestosterone were separated by ion mobility spectrometry prior to mass analysis on the basis of differences in their collision cross sections, which have been measured in nitrogen. Combining ion mobility separation with UPLC/MS enhances the analysis of these low-abundance steroids in urine by selective interrogation of specific retention time, mass-to-charge and mobility regions. Detection limits for the UPLC-IM-MS/MS analysis of TG and ETG were 9.9 ng mL−1and 98 ng mL−1respectively, equivalent to 0.7 ng mL−1and 7.4 ng mL−1in urine, with linear dynamic ranges corresponding to 0.7–108 ng mL−1and 7.4–147 ng mL−1in urine. Repeatability (%RSD) for urine extracts was 0.64% and 2.31% for TG and ETG respectively. [ABSTRACT FROM AUTHOR]

Background:The most common type of ovarian germ cell tumor is the teratoma. Thyroid tissue, both benign and malignant, may be a component of an ovarian teratoma. Here we review this topic and illustrate major features by presenting multimodal management of a patient with BRAF-positive disseminated follicular thyroid cancer arising in an ovarian teratoma.Summary:Malignant thyroid tissue is often difficult to distinguish from benign thyroid tissue arising in ovarian teratomas. Preoperatively, an elevated thyroglobulin (Tg) level, laboratory or clinical evidence of hyperthyroidism, or ultrasonography appearance of “struma pearl” should prompt referral to oncologist for surgical management of a possibly malignant ovarian teratoma. Postoperatively, tumor tissue should be referred to pathologists experienced with differentiating benign from malignant struma ovarii. Once diagnosed, treatment of this rare condition should be handled by a team of specialists with combined treatment modalities. We cared for woman with disseminated thyroid cancer arising in an ovarian teratoma whose history illustrates the complexity of managing ovarian teratomas with malignant thyroid tissue. At age 33 she had an intraoperative rupture of an ovarian cyst, thought to be struma ovarii. During her next pregnancy, pelvic masses were noted; biopsies revealed well-differentiated papillary thyroid carcinoma, follicular variant. She was euthyroid, but had elevated serum Tg levels. Surgical staging demonstrated widely metastatic intraabdominal dissemination. A thyroidectomy revealed no malignancy. A post-131I treatment scan revealed diffuse uptake throughout the abdomen. She then developed abdominal pain and, on computed tomography, was found to have multiple intraabdominal foci of disease. Serum Tg was 264 ng/mL while on L-thyroxine for hypothyroidism and to obtain thyrotropin suppression. A 18 fluorodeoxyglucose positron emission tomography scan showed no pathological uptake. The tumor was found to be BRAFmutation positive (K601E). She underwent extensive secondary debulking and a second course of 131I with lithium pretreatment. Posttreatment scan revealed diffuse abdominal uptake. Six months posttherapy, the patient is asymptomatic with a serum Tg of 18.1 ng/mL.Conclusions:Aggressive multimodal management appears to be the most promising approach for malignant thyroid tissue arising in ovarian teratomas. [ABSTRACT FROM AUTHOR]

Introduction: The quantitative measurement of circulating gut bacteria-derived metabolites has increased in recent years due to their associations with health and disease. While much of the previous attention has been placed on metabolites considered as deleterious to health, a shift to the investigation of short-chain fatty acids (SCFAs) as potential health promotors has been observed. Objectives: To develop a simple, high-throughput and quantitative assay to measure gut-derived SCFAs in clinically relevant biofluids using gas chromatography-mass spectrometry (GC–MS). Methods: A short (7.5 min) GC–MS assay was optimized for measurement of seven straight- and branched-chain SCFAs and their deuterated isotopes using a wax-based column for analysis without prior derivatization. The assay was validated using routine criteria to assess precision, accuracy, matrix effects, recovery, and extraction reproducibility. Assay applicability was tested in cohorts of healthy individuals and kidney disease patients. Results: The assay was demonstrated to be precise, accurate and reproducible with acceptable levels of matrix effect and analyte recovery. Lower limits of detection and quantitation were in the low ng/mL range. An investigation into different blood collection tube chemistries demonstrated that lithium heparin plasma and serum clotting activator tubes are recommended for use in future cross-study comparisons. Kidney disease patient analyses demonstrated variable differences across SCFAs when comparing hemodialysis to earlier stages of chronic kidney disease, demonstrating the suitability of the assay for translation to clinical analyses. Conclusion: The assay has been validated and identified as reliable for use in larger-scale studies for the analysis of SCFAs in human plasma and serum.

ABSTRACT Melorheostosis is a rare dysostosis involving cortical bone overgrowth that affects the appendicular skeleton. Patients present with pain, deformities, contractures, range of motion limitation(s), and limb swelling. It has been described in children as well as adults. We recently identified somatic mosaicism for gain‐of‐function mutations in MAP2K1 in patients with melorheostosis. Despite these advances in genetic understanding, there are no effective therapies or clinical guidelines to help clinicians and patients in disease management. In a study to better characterize the clinical and genetic aspects of the disease, we recruited 30 adults with a radiographic appearance of melorheostosis and corresponding increased uptake on 18F‐NaF positron emission tomography (PET)/CT. Patients underwent physical exam, imaging studies, and laboratory assessment. All patients underwent nerve conduction studies and ultrasound imaging of the nerve in the anatomic distribution of melorheostosis. We found sensory deficits in approximately 77% of patients, with evidence of focal nerve entrapment in five patients. All patients reported pain; 53% of patients had changes in skin overlying the affected bone. No significant laboratory abnormalities were noted. Our findings suggest that patients with melorheostosis may benefit from a multidisciplinary team of dermatologists, neurologists, orthopedic surgeons, pain and palliative care specialists, and physical medicine and rehabilitation specialists. Future studies focused on disease management are needed. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Major depressive disorder (MDD) has been associated with adverse medical consequences, including cardiovascular disease and osteoporosis. Patients with MDD may be classified as having melancholic, atypical, or undifferentiated features. The goal of the present study was to assess whether these clinical subtypes of depression have different endocrine and metabolic features and consequently, varying medical outcomes.Premenopausal women, ages 21 to 45 years, with MDD (N = 89) and healthy controls (N = 44) were recruited for a prospective study of bone turnover. Women with MDD were classified as having melancholic (N = 51), atypical (N = 16), or undifferentiated (N = 22) features. Outcome measures included: metabolic parameters, body composition, bone mineral density (BMD), and 24 hourly sampling of plasma adrenocorticotropin (ACTH), cortisol, and leptin.Compared with control subjects, women with undifferentiated and atypical features of MDD exhibited greater BMI, waist/hip ratio, and whole body and abdominal fat mass. Women with undifferentiated MDD characteristics also had higher lipid and fasting glucose levels in addition to a greater prevalence of low BMD at the femoral neck compared to controls. Elevated ACTH levels were demonstrated in women with atypical features of depression, whereas higher mean 24-hour leptin levels were observed in the melancholic subgroup.Pre-menopausal women with various features of MDD exhibit metabolic, endocrine, and BMD features that may be associated with different health consequences.ClinicalTrials.gov NCT00006180.

An inverse relationship between major depressive disorder (MDD) and bone mineral density (BMD) has been suggested, but prospective evaluation in premenopausal women is lacking.Participants of this prospective study were 21 to 45 year-old premenopausal women with MDD (n = 92) and healthy controls (n = 44). We measured BMD at the anteroposterior lumbar spine, femoral neck, total hip, mid-distal radius, trochanter, and Ward's triangle, as well as serum intact parathyroid hormone (iPTH), ionized calcium, plasma adrenocorticotropic hormone (ACTH), serum cortisol, and 24-hour urinary-free cortisol levels at 0, 6, 12, 24, and 36 months. 25-hydroxyvitamin D was measured at baseline.At baseline, BMD tended to be lower in women with MDD compared to controls and BMD remained stable over time in both groups. At baseline, 6, 12, and 24 months intact PTH levels were significantly higher in women with MDD vs. controls. At baseline, ionized calcium and 25-hydroxyvitamin D levels were significantly lower in women with MDD compared to controls. At baseline and 12 months, bone-specific alkaline phosphatase, a marker of bone formation, was significantly higher in women with MDD vs. controls. Plasma ACTH was also higher in women with MDD at baseline and 6 months. Serum osteocalcin, urinary N-telopeptide, serum cortisol, and urinary free cortisol levels were not different between the two groups throughout the study.Women with MDD tended to have lower BMD than controls over time. Larger and longer studies are necessary to extend these observations with the possibility of prophylactic therapy for osteoporosis.ClinicalTrials.gov NCT 00006180.