A direct analysis method using sheath flow probe electrospray ionisation-mass spectrometry (sfPESI-MS) to detect drug residues from fingerprint forensic gel lifts.

Latent fingerprints at crime scenes are frequently recovered using forensic gel-lifters, which can help to preserve the crime scene and to enhance visualisation of traces such as blood or paint. In addition to providing fingerprint ridge detail, additional chemical information can also be recovered from gel lifts that may prove pertinent to an investigation. However, while DNA and metal ions have been shown to be able to be detected in gel-lifted fingerprints, the determination of other types of chemical information such as the presence of drugs in gel-lifted prints has not been previously shown. This study demonstrates the application of an ambient ionisation method, sheath flow probe electrospray ionisation-mass spectrometry (sfPESI-MS), to the direct analysis of gel-lifted fingerprints. A model drug compound (zolpidem) is successfully detected from gel-lifted prints from three different surface types: glass, metal, and paper. The surface activity-based separation associated with probe electrospray approaches is shown to resolve zolpidem ions from background phthalate species, significantly enhancing the response obtained from the gel-lifter. A depletion series experiment shows that the drug residue can be detected with up to 100% efficiency after eight consecutive contacts; however, detection efficiency drops to 20% after 30 contacts. The developed approach has potential application to analysis of historical gel-lifters to obtain additional chemical information.

Lipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.

A distinct adipose tissue distribution pattern was observed in patients with methylmalonyl-CoA mutase deficiency, an inborn error of branched-chain amino acid (BCAA) metabolism, characterized by centripetal obesity with proximal upper and lower extremity fat deposition and paucity of visceral fat, that resembles familial multiple lipomatosis syndrome. To explore brown and white fat physiology in methylmalonic acidemia (MMA), body composition, adipokines, and inflammatory markers were assessed in 46 patients with MMA and 99 matched controls. Fibroblast growth factor 21 levels were associated with acyl-CoA accretion, aberrant methylmalonylation in adipose tissue, and an attenuated inflammatory cytokine profile. In parallel, brown and white fat were examined in a liver-specific transgenic MMA mouse model (Mmut-/- TgINS-Alb-Mmut). The MMA mice exhibited abnormal nonshivering thermogenesis with whitened brown fat and had an ineffective transcriptional response to cold stress. Treatment of the MMA mice with bezafibrates led to clinical improvement with beiging of subcutaneous fat depots, which resembled the distribution seen in the patients. These studies defined what we believe to be a novel lipodystrophy phenotype in patients with defects in the terminal steps of BCAA oxidation and demonstrated that beiging of subcutaneous adipose tissue in MMA could readily be induced with small molecules.

Differentiation of Body Fluid Stains Using a Portable, Low-Cost Ion Mobility Spectrometry Device-A Pilot Study.

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.

Development of a rapid, in-situ analysis method using sheath-flow probe electrospray ionisation-mass spectrometry for the direct identification of cocaine metabolites in dried blood spots.

RATIONALE: Small amounts of biofluid samples are frequently found at crime scenes; however, existing gold standard methods such as LC-MS frequently require destructive extraction of the sample before a time-consuming analysis which puts strain on forensic analysis providers and can preclude further sample analysis. This study presents the application of sheath-flow probe electrospray ionization-mass spectrometry (sfPESI-MS) to the direct analysis of drug metabolites in dried blood spots (DBS) as a high throughput, minimally destructive alternative. METHODS: A rapid direct analysis method using a sfPESI ionisation source coupled to an Orbitrap Exactive mass spectrometer was applied to detect cocaine metabolites (benzoylecgonine, BZE, cocaethylene, CE, and ecgonine methyl ester, EME) from DBS. An optimisation study exploring the use of different chemical modifiers (formic acid and sodium acetate) in the sfPESI probe extraction solvent was conducted to enhance the sensitivity and reproducibility of the sfPESI-MS method. RESULTS: Optimisation of the extraction solvent significantly enhanced the sensitivity and reproducibility of the sfPESI-MS method. A quantitative response over a five-point calibration range 0.5 to 10 µg/ml was obtained for BZE (R2 = 0.9979) and CE (R2 = 0.9948). Limits of detection (LOD) of 1.31, 0.29 and 0.15 µg/ml were achieved for EME, BZE and CE, respectively, from 48 h aged DBSs with % RSD (relative standard deviation) across the calibration range ranging between 19%-28% for [BZE + H]+ , 13%-21% for [CE + H]+ and 12%-29% for [EME + H]+ . CONCLUSIONS: A rapid (< 20 s) quantitative method for the direct analysis of cocaine metabolites from DBS which requires no prior sample preparation was developed. Although the LOD achieved for BZE (LOD: 0.29 µg/ml) was above the UK threshold limit of exposure for drug driving (0.05 µg/ml), the method may be suitable for use in identifying overdose in forensic analysis.

Visualization of exhaled breath metabolites reveals distinct diagnostic signatures for acute cardiorespiratory breathlessness.

Acute cardiorespiratory breathlessness accounts for one in eight of all emergency hospitalizations. Early, noninvasive diagnostic testing is a clinical priority that allows rapid triage and treatment. Here, we sought to find and replicate diagnostic breath volatile organic compound (VOC) biomarkers of acute cardiorespiratory disease and understand breath metabolite network enrichment in acute disease, with a view to gaining mechanistic insight of breath biochemical derangements. We collected and analyzed exhaled breath samples from 277 participants presenting acute cardiorespiratory exacerbations and aged-matched healthy volunteers. Topological data analysis phenotypes differentiated acute disease from health and acute cardiorespiratory exacerbation subtypes (acute heart failure, acute asthma, acute chronic obstructive pulmonary disease, and community-acquired pneumonia). A multibiomarker score (101 breath biomarkers) demonstrated good diagnostic sensitivity and specificity (≥80%) in both discovery and replication sets and was associated with all-cause mortality at 2 years. In addition, VOC biomarker scores differentiated metabolic subgroups of cardiorespiratory exacerbation. Louvain clustering of VOCs coupled with metabolite enrichment and similarity assessment revealed highly specific enrichment patterns in all acute disease subgroups, for example, selective enrichment of correlated C5-7 hydrocarbons and C3-5 carbonyls in heart failure and selective depletion of correlated aldehydes in acute asthma. This study identified breath VOCs that differentiate acute cardiorespiratory exacerbations and associated subtypes and metabolic clusters of disease-associated VOCs.

Debilitating hip degeneration in trichothiodystrophy: Association with ERCC2/XPD mutations, osteosclerosis, osteopenia, coxa valga, contractures, and osteonecrosis.

Trichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder of DNA repair and transcription with developmental delay and abnormalities in brain, eye, skin, nervous, and musculoskeletal systems. We followed a cohort of 37 patients with TTD at the National Institutes of Health (NIH) from 2001 to 2019 with a median age at last observation of 12 years (range 2-36). Some children with TTD developed rapidly debilitating hip degeneration (DHD): a distinctive pattern of hip pain, inability to walk, and avascular necrosis on imaging. Ten (27%) of the 37 patients had DHD at median age 8 years (range 5-12), followed by onset of imaging findings at median age 9 years (range 5-13). All 10 had mutations in the ERCC2/XPD gene. In 7 of the 10 affected patients, DHD rapidly became bilateral. DHD was associated with coxa valga, central osteosclerosis with peripheral osteopenia of the skeleton, and contractures/tightness of the lower limbs. Except for one patient, surgical interventions were generally not effective at preventing DHD. Four patients with DHD died at a median age of 11 years (range 9-15). TTD patients with ERCC2/XPD gene mutations have a high risk of musculoskeletal abnormalities and DHD leading to poor outcomes. Monitoring by history, physical examination, imaging, and by physical medicine and rehabilitation specialists may be warranted.

Fracture Risk in Pediatric Patients With MEN2B.

CONTEXT: The skeletal phenotype of patients with MEN2B has been described but fracture risk in these patients has not yet been evaluated. OBJECTIVE: This work aims to better delineate fracture risk in patients with multiple endocrine neoplasia type 2B (MEN2B). METHODS: This case series with chart review was conducted at the National Institutes of Health, Pediatric Oncology Branch. A total of 48 patients with MEN2B were identified, with an age range of 5 to 36 years, median of 19; 24 of 48 (50%) patients were female. Medical records, demographic information, available imaging, and laboratory results were reviewed. History up to age 19 was included in the statistical analyses. RESULTS: Of the 48 patients with MEN2B, 20 patients experienced at least one fracture. The majority (n = 18) experienced their first fracture at or before age 19. The observed frequency of fracture occurrence throughout childhood (0-19 years) was 38%, with very little difference between males and females. This frequency is higher than the 9.47 to 36.1 fractures per 1000 persons per year that has been reported in healthy pediatric cohorts in the United States. Less common sites of fracture including vertebral compression fracture and pelvic fractures were observed in patients with MEN2B. CONCLUSION: In this group of patients with MEN2B, there was an increased overall risk of fracture compared to general pediatric cohorts in the United States. Less common sites of fracture were also observed. This suggests a possible effect of an activating RET mutation on bone physiology and warrants further investigation.

Simple, high-throughput measurement of gut-derived short-chain fatty acids in clinically relevant biofluids using gas chromatography-mass spectrometry.

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.

Gastrointestinal Features of 22q11.2 Deletion Syndrome Include Chronic Motility Problems From Childhood to Adulthood.

OBJECTIVES: 22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion syndrome and has a multisystemic presentation including gastrointestinal features that have not yet been fully described. Our aim was to examine lifetime gastrointestinal problems in a large cohort of patients with 22q11.2DS. METHODS: All patients followed in the 22q and You Center at the Children's Hospital of Philadelphia (n = 1421) were retrospectively screened for: 1) age ≥ 17 years, 2) documented chromosomal microdeletion within the 22q11.2 LCR22A-LCR22D region, and 3) sufficient clinical data to characterize the adult gastrointestinal phenotype. Gastrointestinal problems in childhood, adolescence, and adulthood were summarized. Statistical association testing of symptoms against other patient characteristics was performed. RESULTS: Included patients (n = 206; 46% female; mean age, 27 years; median follow-up, 21 years) had similar clinical characteristics to the overall cohort. Genetic distribution was also similar, with 96% having deletions including the critical LCR22A-LCR22B segment (95% in the overall cohort). Most patients experienced chronic gastrointestinal symptoms in their lifetime (91%), but congenital gastrointestinal malformations (3.5%) and gastrointestinal autoimmune diseases (1.5%) were uncommon. Chronic symptoms without anatomic or pathologic abnormalities represented the vast burden of illness. Chronic symptoms in adulthood are associated with other chronic gastrointestinal symptoms and psychiatric comorbidities ( P < 0.01) but not with deletion size or physiologic comorbidities ( P > 0.05). One exception was increased nausea/vomiting in hypothyroidism ( P = 0.002). CONCLUSIONS: Functional gastrointestinal disorders (FGIDs) are a common cause of ill health in children and adults with 22q11.2DS. Providers should consider screening for the deletion in patients presenting with FGIDs and associated comorbidities such as neuropsychiatric illness, congenital heart disease, and palatal abnormalities.

Associations Between Central Obesity and Lifelong Antiviral Therapy in Adults Living With HIV Acquired From Early Childhood.

BACKGROUND: Little is known regarding the long-term effects of antiretroviral (ARV) exposure on body composition for people living with HIV (PLWH) since early childhood. This study explores changes in body fat distribution in relation to ARV exposure. METHODS: We conducted a prospective study of adults with perinatal HIV (n = 70) using dual-energy X-ray absorptiometry and standard anthropometrics. Trunk to limb fat ratio and waist to hip ratio were compared cross-sectionally to 47 matched controls. Furthermore, changes in body composition and ARV exposure were evaluated longitudinally in a subset of 40 PLWH with a median follow-up of 7 years. RESULTS: Cross-sectional comparisons of PLWH with controls revealed significantly higher waist to hip ratio, trunk to limb fat ratio, HOMA-IR, and triglycerides, whereas BMI did not differ. Among PLWH with longitudinal follow-up, the prevalence of overweight increased from 27.5% to 52.5% and obesity from 12.5% to 25%; waist to hip and trunk to limb fat ratios also increased (P < 0.0001). Changes in waist to hip ratio were positively correlated with longer exposure during follow-up to darunavir (r = 0.36; P = 0.02), whereas increases in trunk to limb fat ratio were positively correlated with longer exposure to stavudine (r = 0.39; P = 0.01) and didanosine (r = 0.39; P = 0.01) but inversely associated with emtricitabine (r = -0.33; P = 0.04). Increases in waist to hip ratio were correlated with increases in triglyceride levels (r = 0.35; P = 0.03). CONCLUSION: This study presents strong evidence for persistent and worsening central adiposity in young adults with lifelong HIV and extensive ARV exposure. As this cohort ages, continued evaluation of the body composition and metabolic impact of lifelong ARV therapy is warranted to optimize long-term health.

Osteogenesis Imperfecta: The Impact of Genotype and Clinical Phenotype on Adiposity and Resting Energy Expenditure.

CONTEXT: Mutations in type I collagen or collagen-related proteins cause osteogenesis imperfecta (OI). Energy expenditure and body composition in OI could reflect reduced mobility or intrinsic defects in osteoblast differentiation increasing adipocyte development. OBJECTIVE: This study compares adiposity and resting energy expenditure (REE) in OI and healthy controls (HC), for OI genotype- and Type-associated differences. METHODS: We studied 90 participants, 30 with OI (11 COL1A1 Gly, 8 COL1A2 Gly, 4 COL1A1 non-Gly, 1 COL1A2 non-Gly, 6 non-COL; 8 Type III, 16 Type IV, 4 Type VI, 1 Type VII, 1 Type XIV) and 60 HC with sociodemographic characteristics/BMI/BMIz similar to the OI group. Participants underwent dual-energy x-ray absorptiometry to determine lean mass and fat mass percentage (FM%) and REE. FM% and REE were compared, adjusting for covariates, to examine the relationship of OI genotypes and phenotypic Types. RESULTS: FM% did not differ significantly in all patients with OI vs HC (OI: 36.6% ± 1.9%; HC: 32.7% ± 1.2%; P = 0.088). FM% was, however, greater than HC for those with non-COL variants (P = 0.016). FM% did not differ from HC among OI Types (P values > 0.05).Overall, covariate-adjusted REE did not differ significantly between OI and HC (OI: 1376.5 ± 44.7 kcal/d; HC: 1377.0 ± 96 kcal/d; P = 0.345). However, those with non-COL variants (P = 0.016) and Type VI OI (P = 0.04) had significantly lower REE than HC. CONCLUSION: Overall, patients with OI did not significantly differ in either extra-marrow adiposity or REE from BMI-similar HC. However, reduced REE among those with non-COL variants may contribute to greater adiposity.

Assessment of Osteoporosis and Fracture Risk in Mastocytosis within a North American Cohort.

BACKGROUND: Systemic mastocytosis (SM), a clonal expansion of mast cells affecting multiple organs including the skeletal system, puts patients at risk for osteoporosis and fractures. Various aspects of skeletal disease in SM have been reported among European cohorts. OBJECTIVE: To determine fracture prevalence and risk predictors in SM in a North American (NA) cohort and compare findings with studies of other populations. METHODS: Fifty patients, aged 25-74 years, were grouped based on fracture type and history. Data collected included laboratory findings and radiographic markers such as serum tryptase, bone turnover markers, dual-energy x-ray absorptiometry images, and trabecular bone scores. We performed univariate and multivariate analyses of these findings. RESULTS: Fracture history was found in 74% of patients. Significantly different median age, body mass index, dual-energy x-ray absorptiometry scores, and alkaline phosphatase levels were observed between fracture groups, consistent with French and Dutch studies. Significant findings included the difference in trabecular bone scores among fracture groups, the association between alkaline phosphatase and fracture type and occurrence, and the model for predicting fracture risk based on DXA spine T-scores, alkaline phosphatase, and age (81.3% accuracy and 77.1% sensitivity). CONCLUSIONS: Our findings in an NA cohort are in overall agreement with those reported in European studies of skeletal disease and fracture risk for individuals with SM. We include an interactive calculator designed from a predictive model based on the NA cohort, which may be used for improved screening for fracture risk.

DNA methylation of tumour necrosis factor (TNF) alpha gene is associated with specific blood fatty acid levels in a gender-specific manner.

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.

18F-FDG PET Assessment of Malignant Pleural Mesothelioma: Total Lesion Volume and Total Lesion Glycolysis-The Central Role of Volume.

Cancer survival is related to tumor volume. 18F-FDG PET measurement of tumor volume holds promise but is not yet a clinical tool. Measurements come in 2 forms: the first is total lesion volume (TLV) based on the number of voxels in the tumor, and the second is total lesion glycolysis (TLG), which is the TLV multiplied by the average SUL (i.e., SUV normalized for lean mass) of the tumor (SULaverage). In this study, we measured tumor volume in patients with malignant pleural mesothelioma (MPM). Methods: A threshold-based program in Interactive Data Language was developed to measure tumor volume in 18F-FDG PET images. Nineteen patients with MPM were studied before and after 2 cycles (6 wk) of chemoimmunotherapy. Measurements included TLV, TLG, the sum of the SULs in the tumor (SULtotal, a measure of total 18F-FDG uptake), and SULaverageResults: Baseline TLV ranged from 11 to 2,610 cm3 TLG ranged from 32 to 8,552 cm3 g/mL and correlated strongly with TLV. Although tumor volumes ranged over 3 orders of magnitude, SULaverage stayed within a narrow range of 2.4-5.3 units. Thus, TLV was the major component of TLG, whereas SULaverage was a minor component and was essentially constant. Further evaluation of SULaverage showed that in this cohort its 2 components, SULtotal and TLV, changed in parallel and were strongly correlated (r = 0.99, P < 0.01). Thus, whether the tumors were large or small, 18F-FDG uptake as measured by SULtotal was proportional to the TLV. Conclusion: TLG equals TLV multiplied by SULaverage, essentially TLV multiplied by a constant. Thus TLG, commonly considered a measure of metabolic activity in tumors, is also in this cohort a measure of tumor volume. The constancy of SULaverage is due to the fact that 18F-FDG uptake is proportional to tumor volume. Thus, in this study, 18F-FDG uptake was also a measure of volume.

Clinical Evaluation of Melorheostosis in the Context of a Natural History Clinical Study.

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.

Weight-based teasing is associated with gain in BMI and fat mass among children and adolescents at-risk for obesity: A longitudinal study.

BACKGROUND: Youths with overweight and obesity report frequent instances of weight-based teasing. However, little is known about the prospective associations between weight-based teasing and changes in body composition among youth. OBJECTIVE: To assess associations between weight-based teasing and changes in body mass index (BMI) and fat mass in a longitudinal study of youths with, or at-risk for, overweight and obesity. METHODS: One hundred ten youths with, or at-risk for, overweight participated in a longitudinal observational study. The Perception of Teasing Scale was administered at baseline. Height, weight, and body composition were obtained at baseline and at follow-ups (range: 1-15 years). RESULTS: Mean age at baseline was 11.8 years; 53% had overweight/obesity; 36% were non-Hispanic Black; 55% were female; mean follow-up from baseline: 8.5 years. Adjusting for covariates and repeated measures of BMI or fat mass, linear mixed models revealed that weight-based teasing was associated with greater gain of BMI and fat mass across the follow-up period (ps ≤ .007). Adjusting for covariates, youths reporting high weight-based teasing (two standard deviations above the mean) experienced a 33% greater gain in BMI (an additional 0.20 kg/m2 ) and a 91% greater gain in fat mass (an additional 0.65 kg) per year compared with peers who reported no weight-based teasing. CONCLUSIONS: Among youths with, and at-risk for, overweight and obesity, weight-based teasing was associated with greater weight and fat gain.

Combined hydrophilic interaction liquid chromatography-scanning field asymmetric waveform ion mobility spectrometry-time-of-flight mass spectrometry for untargeted metabolomics.

Untargeted metabolite profiling of biological samples is a challenge for analytical science due to the high degree of complexity of biofluids. Isobaric species may also not be resolved using mass spectrometry alone. As a result of these factors, many potential biomarkers may not be detected or are masked by co-eluting interferences in conventional LC-MS metabolomic analyses. In this study, a comprehensive liquid chromatography-mass spectrometry workflow incorporating a fast-scanning miniaturised high-field asymmetric waveform ion mobility spectrometry separation (LC-FAIMS-MS) is applied to the untargeted metabolomic analysis of human urine. The time-of-flight mass spectrometer used in the study was scanned at a rate of 20 scans s-1 enabling a FAIMS CF spectrum to be acquired within a 1-s scan time, maintaining an adequate number of data points across each LC peak. The developed method is demonstrated to be able to resolve co-eluting isomeric species and shows good reproducibility (%RSD < 4.9%). The nested datasets obtained for fresh, aged, and QC urine samples were submitted for multivariate statistical analysis. Seventy unique biomarker ions showing a statistically significant difference between fresh and aged urine were identified with optimal transmission CF values obtained across the full CF spectrum. The potential of using FAIMS to select ions for in-source collision-induced dissociation is demonstrated for FAIMS-selected methylxanthine ions yielding characteristic fragment ion species indicative of the precursor. Graphical abstract.

Open-Label Clinical Trials of Oral Pulse Dexamethasone for Adults with Idiopathic Nephrotic Syndrome.

BACKGROUND: In adults with primary focal segmental glomerulosclerosis (FSGS), daily prednisone may induce complete remissions (CR) and partial remissions (PR), but relapses are frequent and adverse events are common. METHODS: We carried out 2 open-label, uncontrolled trials to explore the efficacy and tolerability of pulse oral dexamethasone as an alternative to daily prednisone. We enrolled adult patients with proteinuria > 3.5 g/day despite the use of renin-angiotensin-aldosterone blockade. In the first trial, we enrolled 14 subjects with FSGS and administered 4 dexamethasone doses (25 mg/m2) daily for 4 days, repeated every 28 days over 32 weeks. The second trial involved a more intensive regimen. Eight subjects received 4 dexamethasone doses of 50 mg/m2 every 4 weeks for 12 weeks, followed by 4 doses of 25 mg/m2 every 4 weeks for 36 weeks; subjects were randomized to 2 doses every 2 weeks or 4 doses every 4 weeks. RESULTS: In the first trial, we enrolled 13 subjects with FSGS and 1 with minimal change disease and found a combined CR and PR rate of 36%. In the second trial, we enrolled 8 subjects. The combined CR and PR rate was 29%. Analysis combining both trials showed a combined CR and PR rate of 33%. Adverse events were observed in 32% of subjects, with mood symptoms being most common. There were no serious adverse events related to the study. CONCLUSION: We conclude that high dose oral dexamethasone is well tolerated by adults with idiopathic nephrotic syndrome and may have some efficacy.

Transforming presumptive forensic testing: in situ identification and age estimation of human bodily fluids.

The ability to achieve rapid, in situ identification and age estimation of human bodily fluids can provide valuable information during the investigation of a crime. A novel direct analysis method now permits the rapid in situ identification and age estimation of human bodily fluids for forensic analysis at crime scenes. A thermal desorption surface sampling probe was developed and coupled with a compact mass spectrometer for the direct analysis of volatile organic compound (VOC) profiles of human bodily fluids within two months and in different environmental conditions, without the need for prior sample preparation. The method is not only capable of identifying bodily fluids and discriminating against common interferent species, but also differentiating between bodily fluid stains of different ages over a time period of two months. This demonstrates the potential for rapid in situ identification and age estimation of bodily fluids without the need for contaminative presumptive tests or time-consuming sample preparation.