Trio RNA sequencing in a cohort of medically complex children.

Genome sequencing (GS) is a powerful test for the diagnosis of rare genetic disorders. Although GS can enumerate most non-coding variation, determining which non-coding variants are disease-causing is challenging. RNA sequencing (RNA-seq) has emerged as an important tool to help address this issue, but its diagnostic utility remains understudied, and the added value of a trio design is unknown. We performed GS plus RNA-seq from blood using an automated clinical-grade high-throughput platform on 97 individuals from 39 families where the proband was a child with unexplained medical complexity. RNA-seq was an effective adjunct test when paired with GS. It enabled clarification of putative splice variants in three families, but it did not reveal variants not already identified by GS analysis. Trio RNA-seq decreased the number of candidates requiring manual review when filtering for de novo dominant disease-causing variants, allowing for the exclusion of 16% of gene-expression outliers and 27% of allele-specific-expression outliers. However, clear diagnostic benefit from the trio design was not observed. Blood-based RNA-seq can facilitate genome analysis in children with suspected undiagnosed genetic disease. In contrast to DNA sequencing, the clinical advantages of a trio RNA-seq design may be more limited.

Precision cut intestinal slices, a novel model of acute food allergic reactions.

BACKGROUND: Food allergy affects up to 10% of the pediatric population. Despite ongoing efforts, treatment options remain limited. Novel models of food allergy are needed to study response patterns downstream of IgE-crosslinking and evaluate drugs modifying acute events. Here, we report a novel human ex vivo model that displays acute, allergen-specific, IgE-mediated smooth muscle contractions using precision cut intestinal slices (PCIS). METHODS: PCIS were generated using gut tissue samples from children who underwent clinically indicated surgery. Viability and metabolic activity were assessed from 0 to 24 h. Distribution of relevant cell subsets was confirmed using single nucleus RNA sequencing. PCIS were passively sensitized using plasma from peanut allergic donors or peanut-sensitized non-allergic donors, and exposed to various stimuli including serotonin, histamine, FcɛRI-crosslinker, and food allergens. Smooth muscle contractions and mediator release functioned as readouts. A novel program designed to measure contractions was developed to quantify responses. The ability to demonstrate the impact of antihistamines and immunomodulation from peanut oral immunotherapy (OIT) was assessed. RESULTS: PCIS viability was maintained for 24 h. Cellular distribution confirmed the presence of key cell subsets including mast cells. The video analysis tool reliably quantified responses to different stimulatory conditions. Smooth muscle contractions were allergen-specific and reflected the clinical phenotype of the plasma donor. Tryptase measurement confirmed IgE-dependent mast cell-derived mediator release. Antihistamines suppressed histamine-induced contraction and plasma from successful peanut OIT suppressed peanut-specific PCIS contraction. CONCLUSION: PCIS represent a novel human tissue-based model to study acute, IgE-mediated food allergy and pharmaceutical impacts on allergic responses in the gut.

X-linked myotubular myopathy is associated with epigenetic alterations and is ameliorated by HDAC inhibition.

X-linked myotubular myopathy (XLMTM) is a fatal neuromuscular disorder caused by loss of function mutations in MTM1. At present, there are no directed therapies for XLMTM, and incomplete understanding of disease pathomechanisms. To address these knowledge gaps, we performed a drug screen in mtm1 mutant zebrafish and identified four positive hits, including valproic acid, which functions as a potent suppressor of the mtm1 zebrafish phenotype via HDAC inhibition. We translated these findings to a mouse XLMTM model, and showed that valproic acid ameliorates the murine phenotype. These observations led us to interrogate the epigenome in Mtm1 knockout mice; we found increased DNA methylation, which is normalized with valproic acid, and likely mediated through aberrant 1-carbon metabolism. Finally, we made the unexpected observation that XLMTM patients share a distinct DNA methylation signature, suggesting that epigenetic alteration is a conserved disease feature amenable to therapeutic intervention.

The effect of leading edge porosity on airfoil turbulence interaction noise.

Airfoil turbulence interaction noise and the flow field up to and over the porous leading edge is experimentally studied. The porous leading edges were of the same base triply periodic minimal surface structure with varying porosity to enable us to understand how the porosity, permeability, and pore size affect the generated turbulence interaction noise. The turbulent flow was generated by means of a passive turbulence grid that does not affect the normal background noise of the wind tunnel. Far-field noise results were obtained from a polar microphone array to assess the directivity of the sound as well as the narrowband frequency contributions. Far-field noise results demonstrate that increasing porosity reduces the turbulence interaction noise over low-to-mid frequencies, with a penalty of a high frequency noise increase. Flow measurement results indicate hydrodynamic penetration of the flow into the porous structure at the leading edge. Furthermore, the two-point correlation analysis of the velocity fluctuations approaching the leading edge shows that the turbulent structures approaching the solid leading edge appear to deform into more two-dimensional structures, whereas in the case of the porous leading edge, the turbulent structures appear to retain a strong spanwise coherence up to the point of hydrodynamic penetration.

Modeling the conversion between specific IgE test platforms for nut allergens in children and adolescents.

BACKGROUND: Multiplex tests allow for measurement of allergen-specific IgE responses to multiple extracts and molecular allergens and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta-analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen-specific IgE to peanut/tree nut allergens from three IgE test platforms. METHODS: Plasma from Canadian and Austrian children/adolescents with peanut/tree nut sensitization and a cohort of sensitized, high-risk, pre-school asthmatics (total n = 166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer version 1 (ALEX) (Macro Array Dx), MeDALL-chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n = 51) and ImmunoCAP (Thermo Fisher) (n = 62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra-test correlations between PR-10 and nsLTP allergens were assessed. RESULTS: Using two regression methods, we demonstrated the ability to model allergen-specific relationships with acceptable measures of fit (r2  = 94%-56%) for peanut and tree nut sIgE testing at the extract and molecular-level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, and Cor a 9. CONCLUSION: Our models support the notion that quantitative conversion is possible between sIgE multiplex platforms for extracts and molecular allergens and may provide options to aggregate data for future meta-analysis.

Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study.

BACKGROUND: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed. OBJECTIVE: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies. METHODS: The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63+ basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed allergic status in a blinded fashion to develop a generalizable statistical model for comparison to extract and marker allergen-specific IgE. RESULTS: A mixed effect model integrating BAT results for 10 and 100 ng/mL of peanut and individual tree nut extracts was optimal. The area under the ROC curve (AUROC) was 0.98 for peanut, 0.97 for cashew, 0.92 for hazelnut, 0.95 for pistachio, and 0.97 for walnut. The BAT outperformed sIgE testing for peanut or hazelnut and was comparable for walnut (AUROC 0.95, 0.94, 0.92) in a sub-analysis in sensitized patients undergoing OFC. CONCLUSIONS: Basophil activation test can predict allergic clinical status to peanut and tree nuts in multi-nut-sensitized children and may reduce the need for high-risk OFCs in patients.

"One size does not fit all" - lessons learned from a multiple-methods study of a resident wellness curriculum across sites and specialties.

BACKGROUND: There is growing recognition that wellness interventions should occur in context and acknowledge complex contributors to wellbeing, including individual needs, institutional and cultural barriers to wellbeing, as well as systems issues which propagate distress. The authors conducted a multiple-methods study exploring contributors to wellbeing for junior residents in diverse medical environments who participated in a brief resilience and stress-reduction curriculum, the Stress Management and Resiliency Training Program for Residents (SMART-R). METHODS: Using a waitlist-controlled design, the curriculum was implemented for post-graduate year (PGY)-1 or PGY-2 residents in seven residency programs across three sites. Every three months, residents completed surveys, including the Perceived Stress Scale-10, General Self-Efficacy Questionnaire, a mindfulness scale (CAMSR), and a depression screen (PHQ-2). Residents also answered free-text reflection questions about psychological wellbeing and health behaviors. RESULTS: The SMART-R intervention was not significantly associated with decreased perceived stress. Linear regression modeling showed that depression was positively correlated with reported stress levels, while male sex and self-efficacy were negatively correlated with stress. Qualitative analysis elucidated differences in these groups: Residents with lower self-efficacy, those with a positive depression screen, and/or female residents were more likely to describe experiencing lack of control over work. Residents with higher self-efficacy described more positive health behaviors. Residents with a positive depression screen were more self-critical, and more likely to describe negative personal life events. CONCLUSIONS: This curriculum did not significantly modify junior residents' stress. Certain subpopulations experienced greater stress than others (female residents, those with lower self-efficacy, and those with a positive depression screen). Qualitative findings from this study highlight universal stressful experiences early in residency, as well as important differences in experience of the learning environment among subgroups. Tailored wellness interventions that aim to support diverse resident sub-groups may be higher yield than a "one size fits all" approach. TRIAL REGISTRATION: NCT02621801 , Registration date: December 4, 2015 - Retrospectively registered.

High-resolution profiling of NMD targets in yeast reveals translational fidelity as a basis for substrate selection.

Nonsense-mediated mRNA decay (NMD) plays an important role in eukaryotic gene expression, yet the scope and the defining features of NMD-targeted transcripts remain elusive. To address these issues, we reevaluated the genome-wide expression of annotated transcripts in yeast cells harboring deletions of the UPF1, UPF2, or UPF3 genes. Our new RNA-seq analyses confirm previous results of microarray studies, but also uncover hundreds of new NMD-regulated transcripts that had escaped previous detection, including many intron-containing pre-mRNAs and several noncoding RNAs. The vast majority of NMD-regulated transcripts are normal-looking protein-coding mRNAs. Our bioinformatics analyses reveal that this set of NMD-regulated transcripts generally have lower translational efficiency and higher ratios of out-of-frame translation. NMD-regulated transcripts also have lower average codon optimality scores and higher transition probability to nonoptimal codons. Collectively, our results generate a comprehensive catalog of yeast NMD substrates and yield new insights into the mechanisms by which these transcripts are targeted by NMD.

Assessment of Physical Fitness after Bariatric Surgery and Its Association with Protein Intake and Type of Cholecalciferol Supplementation.

: Background: Several studies showed that there is a relationship between vitamin and mineral status and muscle strength. In particular this is the case for handgrip strength (HS) and vitamin D deficiency. In bariatric surgery there is a risk of decrease in muscle strength after surgery and also vitamin and mineral deficiencies are not uncommon. The aim of this study is to assess the effect of low vitamin 25 (OH) cholecalciferol levels, high dose cholecalciferol supplementation regime and protein intake on physical fitness, measured using handgrip strength (HS) and the shuttle walk run test (SWRT). Methods: For this retrospective study, 100 patients who have had bariatric surgery were included. Group A (n = 50) used 800 IU oral cholecalciferol per day. Group B (n = 50) used 800 IU oral cholecalciferol daily and 50,000 IU liquid cholecalciferol monthly lifelong. Both groups were matched on common variables. To measure physical fitness, we used the HS manometer of Jamar and the Shuttle Walk Run Test (SWRT) to assess physical capacity. Results: No significant differences in HS and SWRT outcomes were found between patients with serum 25 (OH) cholecalciferol < 75 nmol/L or >75 nmol/L. The postoperative HS is significantly influenced by protein intake (p = 0.017) and no significant influence was seen in outcomes of the SWRT (p = 0.447). Conclusion: We have found that serum 25 (OH) cholecalciferol and different cholecalciferol supplementation regimes do not have a significant effect on HS and SWRT before, three and 6 months after surgery. It seems that protein intake plays a more important role in maintaining adequate muscle strength.

SMART-R: A Prospective Cohort Study of a Resilience Curriculum for Residents by Residents.

OBJECTIVE: This study aimed to determine the feasibility of a resident-led resiliency curriculum developed by residents, for residents. METHODS: The Stress Management and Resiliency Training Program for Residents (SMART-R) is a 6-h group-based curriculum that teaches meditation, behavioral skills, and positive perspective-taking strategies. SMART-R was implemented for all medicine and psychiatry interns at a large US teaching hospital during the first 6 months of internship. Risk and resilience factors for burnout were assessed before and after the curriculum. A wearable health-tracking device was used to assess feasibility of wearables for studying resident health behaviors. RESULTS: All 73 medicine and 17 psychiatry interns participated in the SMART-R curriculum. Seventy-five of 85 interns (88%) consented to be in the study. Thirty-one of 75 (41%) completed both baseline and post surveys of risk and resilience factors for burnout. Preliminary curriculum feedback was enthusiastic. Twenty-five of 62 (40%) wore the health tracker more than half the time in the first 3 months of the study. CONCLUSIONS: Implementation of a resident-led resiliency curriculum for internal medicine and psychiatry interns at an academic medical center during the most challenging first months of internship is feasible. Future controlled studies are needed to determine efficacy of SMART-R on risk and resilience factors. Over the first 6 months of internship, we observed an expected increase in burnout, fatigue, and depression, though other key risk and resilience factors were unchanged.

NMD monitors translational fidelity 24/7.

Nonsense-mediated mRNA decay (NMD) is generally thought to be a eukaryotic mRNA surveillance pathway tasked with the elimination of transcripts harboring an in-frame premature termination codon (PTC). As presently conceived, NMD acting in this manner minimizes the likelihood that potentially toxic polypeptide fragments would accumulate in the cytoplasm. This notion is to be contrasted to the results of systematic RNA-Seq and microarray analyses of NMD substrates in multiple model systems, two different experimental approaches which have shown that many mRNAs identified as NMD substrates fail to contain a PTC. Our recent results provide insight into, as well as a possible solution for, this conundrum. By high-resolution profiling of mRNAs that accumulate in yeast when the principal NMD regulatory genes (UPF1, UPF2, and UPF3) are deleted, we identified approximately 900 NMD substrates, the majority of which are normal-looking mRNAs that lack PTCs. Analyses of ribosomal profiling data revealed that the latter mRNAs tended to manifest elevated rates of out-of-frame translation, a phenomenon that would lead to premature translation termination in alternative reading frames. These results, and related observations of heterogeneity in mRNA isoforms, suggest that NMD should be reconsidered as a probabilistic mRNA quality control pathway that is continually active throughout an mRNA's life cycle.

Risk and Resilience Factors Associated with Resident Burnout.

OBJECTIVE: We investigated hypothesized risk and resilience factors and their association with burnout in first year medicine and psychiatry residents at an urban teaching hospital in order to help guide the development of interventions targeted at reducing burnout. METHODS: We administered the Maslach Burnout Inventory (MBI), Perceived Stress Scale-10, Functional Assessment of Chronic Illness Therapy-Fatigue Scale, Penn State Worry Questionnaire, Patient Health Questionnaire-9 (depression symptoms), Revised Life Orientation Test (optimism), Self-Efficacy Questionnaire, Cognitive and Affective Mindfulness Scale, Interpersonal Reactivity Index Perspective-Taking Scale (empathy), and Measure of Current Status-Part A to first year medicine and psychiatry residents prior to initiation of clinical rotations in June. RESULTS: The response rate was 91 % (68 of 75 residents). Nineteen respondents (28 %) met criteria for burnout as measured by the MBI. Residents with burnout scored higher on self-report measures assessing perceived stress (Cohen's d = 0.97; p = 0.004), fatigue (d = 0.79; p = 0.018), worry (d = 0.88; p = 0.0009), and depression symptoms (d = 0.84; p = 0.035) and scored lower on questionnaires assessing mindfulness (d = -0.63; p = 0.029) and coping ability (d = -0.79; p = 0.003). CONCLUSIONS: In a cross-sectional assessment using self-report measures, we found that nearly a third of first year residents prior to starting their internships experience burnout. They exhibit lower levels of mindfulness and coping skills and higher levels of depression symptoms, fatigue, worry, and stress. These preliminary findings should encourage programs to initiate and study curricula that combine mindfulness and self-awareness coping strategies to enhance or protect against burnout as well as cognitive behavioral coaching strategies to offset symptoms of burnout when present.

The Relation of Religious Attitudes and Behaviours with Depression in Boarding Quran Course Students.

BACKGROUND: Boarding Quran courses are religious institutions where course attendees spend large part of the year. Depression is an ever-increasing health problem. So, it is worth to study on the effects of religion concept and religious belief and behaviours' that religion concept brings, on depression. The main purpose of this study, is to analyse the effect of religious attitudes and behaviours on depression in Quran course / hafiz students. SUBJECTS AND METHODS: The study is a cross sectional, case-control survey research. Boarding Quran courses and high schools were visited in Samsun city. A total of 956 participants enrolled between June 2015 and December 2015 were included into study from Samsun city of Turkey. Volunteers, 13 years and over ones without any psychiatric disorders were included in the study. Religious attitude-behaviour inventory and Beck's depression inventory were used in the study. RESULTS: Median point of case group attitude scale was 49, control group's was 57 and difference among both has a statistical meaning (p<0.001). Beck's depression score average of case group is 12.93±9.33, its control group's average is 13.74±11.14 and difference between them is not important. Median score of both groups are 11. When scores of attitude and depression scales compared with each other in terms of demographic parameters, there is a difference among group, gender, age and education parameters (p<0.001). CONCLUSIONS: It was seen that religious attitudes and behaviours can be protective for boarding Quran course students but it cannot be enough by itself.

The Genomic Architecture of Pregnancy-Associated Plasticity in the Maternal Mouse Hippocampus.

Pregnancy is associated with extraordinary plasticity in the maternal brain. Studies in humans and other mammals suggest extensive structural and functional remodeling of the female brain during and after pregnancy. However, we understand remarkably little about the molecular underpinnings of this natural phenomenon. To gain insight into pregnancy-associated hippocampal plasticity, we performed single nucleus RNA sequencing (snRNA-seq) and snATAC-seq from the mouse hippocampus before, during, and after pregnancy. We identified cell type-specific transcriptional and epigenetic signatures associated with pregnancy and postpartum adaptation. In addition, we analyzed receptor-ligand interactions and transcription factor (TF) motifs that inform hippocampal cell type identity and provide evidence of pregnancy-associated adaption. In total, these data provide a unique resource of coupled transcriptional and epigenetic data across a dynamic time period in the mouse hippocampus and suggest opportunities for functional interrogation of hormone-mediated plasticity.

Natural history of a mouse model of X-linked myotubular myopathy.

X-linked myotubular myopathy (XLMTM) is a severe monogenetic disorder of the skeletal muscle. It is caused by loss-of-expression/function mutations in the myotubularin (MTM1) gene. Much of what is known about the disease, as well as the treatment strategies, has been uncovered through experimentation in pre-clinical models, particularly the Mtm1 gene knockout mouse line (Mtm1 KO). Despite this understanding, and the identification of potential therapies, much remains to be understood about XLMTM disease pathomechanisms, and about the normal functions of MTM1 in muscle development. To lay the groundwork for addressing these knowledge gaps, we performed a natural history study of Mtm1 KO mice. This included longitudinal comparative analyses of motor phenotype, transcriptome and proteome profiles, muscle structure and targeted molecular pathways. We identified age-associated changes in gene expression, mitochondrial function, myofiber size and key molecular markers, including DNM2. Importantly, some molecular and histopathologic changes preceded overt phenotypic changes, while others, such as triad structural alternations, occurred coincidentally with the presence of severe weakness. In total, this study provides a comprehensive longitudinal evaluation of the murine XLMTM disease process, and thus provides a critical framework for future investigations.

Variants in ASPH cause exertional heat illness and are associated with malignant hyperthermia susceptibility.

Exertional heat illness (EHI) and malignant hyperthermia (MH) are life threatening conditions associated with muscle breakdown in the setting of triggering factors including volatile anesthetics, exercise, and high environmental temperature. To identify new genetic variants that predispose to EHI and/or MH, we performed genomic sequencing on a cohort with EHI/MH and/or abnormal caffeine-halothane contracture test. In five individuals, we identified rare, pathogenic heterozygous variants in ASPH, a gene encoding junctin, a regulator of excitation-contraction coupling. We validated the pathogenicity of these variants using orthogonal pre-clinical models, CRISPR-edited C2C12 myotubes and transgenic zebrafish. In total, we demonstrate that ASPH variants represent a new cause of EHI and MH susceptibility.

The effects of glucagon like peptide-1 (GLP-1) on cardiac remodeling: exploring the role of medication and physiological modulation after metabolic surgery.

Obesity and associated comorbidities reach epidemic proportions nowadays. Several treatment strategies exist, but bariatric surgery has the only longstanding effects. Since a few years, there is increasing interest in the effects of gastro-intestinal hormones, in particular Glucagon-Like Peptide-1 (GLP-1) on the remission of Type 2 Diabetes (T2DM) and its effects on cardiac cardiovascular morbidity, cardiac remodeling, and mortality. In the past years several high quality multicenter randomized controlled trials were developed to assess the effects of GLP-1 receptor agonist therapy on cardiovascular morbidity and mortality. Most of the trials were designed and powered as non-inferiority trials to demonstrate cardiovascular safety. Most of these trials show a reduction in cardiovascular morbidity in patients with T2DM. Some follow-up studies indicate potential beneficial effects of GLP-1 receptor agonists on cardiovascular function in patients with heart failure, however the results are contradictory, and we need long-term studies to make firm conclusions about the pleiotropic properties of incretin-based therapies. However, it seems that GLP-1 receptor agonists have different effects than the increased GLP-1 production after bariatric surgery on cardiovascular remodeling. One of the hypotheses is that the blood concentrations of GLP-1 receptor agonists are three times higher compared to GLP-1 increase after bariatric and metabolic surgery. The purpose of this narrative review is to summarize the effects of GLP-1 on cardiovascular morbidity, mortality and remodeling due to medication but also due to bariatric and metabolic surgery. The second objective is to explain the possible differences in effects of GLP-1 agonists and bariatric and metabolic surgery.

Effects of Bariatric Surgery on Heart Rhythm Disorders: a Systematic Review and Meta-Analysis.

The aim of this systematic review is to provide an overview of the literature on the effects of bariatric surgery on obesity-associated electrocardiogram (ECG) abnormalities and cardiac arrhythmias. Fourteen studies were included with a methodological quality ranging from poor to good. Majority of the studies showed a significant decrease of QT interval and related measures after bariatric surgery. Seven studies were included in the meta-analysis on effects of bariatric surgery on QTc interval and a significant decrease in QTc interval of - 33.6 ms, 95%CI [- 49.8 to - 17.4] was seen. Bariatric surgery results in significant decrease in QTc interval and P-wave dispersion, i.e., a normalization of initial pathology. The effects on atrial fibrillation are conflicting and not yet fully understood.

Expression of polyamine and SSAT (spermidine/spermine N-1 acetyl transferase) levels following surgical trauma and sepsis.

Polyamines have counterregulatory effects against inflammation, and whole blood polyamine concentrations reflect whole body polyamine levels. The purpose of this study was to investigate changes in blood polyamine concentrations during sublethal surgical damage and sepsis. Eight-week-old CDF1 male mice were used. Sepsis was induced by intraperitoneal injection of lipopolysaccharide, surgical trauma was induced by cecal ligation, and control mice were sham-operated. At 1, 2, 4, 6, and 12 hours following each procedure, polyamine concentrations, tumor necrosis factor (TNF), interleukin 6 (IL-6), and expression of spermidine/spermine N-acetyl transferase (SSAT) in blood cells were measured. Increases in serum TNF and IL-6 were noted in all groups. These increases were most prominent in the sepsis group, followed by the cecal ligation group. The increase in SSAT levels was noted in the sepsis and cecal ligation groups 2 hours after treatment. SSAT expression declined to lowest levels at the sixth hour and slightly re-increased at the 12th hour. Blood levels of putrescine, spermidine, and spermine were stable in all groups. We conclude that blood concentrations of metabolically active polyamines show an early decrease during inflammation. We further conclude that their levels are strictly controlled and are stable after surgical trauma and under septic conditions.