Imaging studies in adults with irritable bowel syndrome (IBS) have shown both morphological and resting state (RS) functional connectivity (FC) alterations related to cortical modulation of sensory ...processing. Because analogous differences have not been adequately investigated in children, this study compared gray matter volume (GMV) and RS-FC between girls with IBS and healthy controls (HC) and tested the correlation between brain metrics and laboratory-based pain thresholds (Pth).
Girls with Rome III criteria IBS (n = 32) and matched HCs (n = 26) were recruited. In a subset of patients, Pth were determined using a thermode to the forearm. Structural and RS scans were acquired. A voxel-based general linear model, adjusting for age, was applied to compare differences between groups. Seeds were selected from regions with group GMV differences for a seed-to-voxel whole brain RS-FC analysis. Significance for analyses was considered at p < .05 after controlling for false discovery rate. Significant group differences were correlated with Pth.
Girls with IBS had lower GMV in the thalamus, caudate nucleus, nucleus accumbens, anterior midcingulate (aMCC), and dorsolateral prefrontal cortex. They also exhibited lower RS-FC between the aMCC and the precuneus, but greater connectivity between the caudate nucleus and precentral gyrus. Girls with IBS had higher Pth with a moderate effect size (t(22.81) = 1.63, p = .12, d = 0.64) and lower thalamic GMV bilaterally was correlated with higher Pth (left: r = -.62, p(FDR) = .008; right: r = -.51, p(FDR) = .08).
Girls with IBS had lower GMV in the PFC, basal ganglia, and aMCC, as well as altered FC between multiple brain networks, suggesting that structural changes related to IBS occur early in brain development. Girls with IBS also showed altered relationships between pain sensitivity and brain structure.
Irritable bowel syndrome (IBS) is a common disorder of brain-gut interactions characterized by chronic abdominal pain, altered bowel movements, often accompanied by somatic and psychiatric ...comorbidities. We aimed to test the hypothesis that a baseline phenotype composed of multi-modal neuroimaging and clinical features predicts clinical improvement on the IBS Symptom Severity Scale (IBS-SSS) at 3 and 12 months without any targeted intervention. Female participants (N = 60) were identified as "improvers" (50-point decrease on IBS-SSS from baseline) or "non-improvers." Data integration analysis using latent components (DIABLO) was applied to a training and test dataset to determine whether a limited number of sets of multiple correlated baseline'omics data types, including brain morphometry, anatomical connectivity, resting-state functional connectivity, and clinical features could accurately predict improver status. The derived predictive models predicted improvement status at 3-months and 12-months with 91% and 83% accuracy, respectively. Across both time points, non-improvers were classified as having greater correlated morphometry, anatomical connectivity and resting-state functional connectivity characteristics within salience and sensorimotor networks associated with greater pain unpleasantness, but lower default mode network integrity and connectivity. This suggests that non-improvers have a greater engagement of attentional systems to perseverate on painful visceral stimuli, predicting IBS exacerbation. The ability of baseline multimodal brain-clinical signatures to predict symptom trajectories may have implications in guiding integrative treatment in the age of precision medicine, such as treatments targeted at changing attentional systems such as mindfulness or cognitive behavioral therapy.
The aim of this study was to determine cardiac arrest- and extracorporeal membrane oxygenation-related risk factors associated with unfavorable outcomes after extracorporeal cardiopulmonary ...resuscitation.
We performed an analysis of merged data from the Extracorporeal Life Support Organization and the American Heart Association Get With the Guidelines-Resuscitation registries.
A total of 32 hospitals reporting to both registries between 2000 and 2014.
Children younger than 18 years old who suffered in-hospital cardiac arrest and underwent extracorporeal cardiopulmonary resuscitation.
None.
Of the 593 children included in the final cohort, 240 (40.5%) died prior to decannulation from extracorporeal membrane oxygenation and 352 (59.4%) died prior to hospital discharge. A noncardiac diagnosis and preexisting renal insufficiency were associated with increased odds of death (adjusted odds ratio, 1.85 95% CI, 1.19-2.89 and 4.74 95% CI, 2.06-10.9, respectively). The median time from onset of the cardiopulmonary resuscitation event to extracorporeal membrane oxygenation initiation was 48 minutes (interquartile range, 28-70 min). Longer time from onset of the cardiopulmonary resuscitation event to extracorporeal membrane oxygenation initiation was associated with higher odds of death prior to hospital discharge (adjusted odds ratio for each 5 additional minutes of cardiopulmonary resuscitation prior to extracorporeal membrane oxygenation initiation, 1.04 95% CI, 1.01-1.07). Each individual adverse event documented during the extracorporeal membrane oxygenation course, including neurologic, pulmonary, renal, metabolic, cardiovascular and hemorrhagic, was associated with higher odds of death, with higher odds as the cumulative number of documented adverse events during the extracorporeal membrane oxygenation course increased.
Outcomes after extracorporeal cardiopulmonary resuscitation reported by linking two national registries are encouraging. Noncardiac diagnoses, preexisting renal insufficiency, longer time from onset of the cardiopulmonary resuscitation event to extracorporeal membrane oxygenation initiation, and adverse events during the extracorporeal membrane oxygenation course are associated with worse outcomes.
Phycoerythrin (PE) is green light-absorbing pigment-protein that assists in efficient light harvesting in cyanobacteria and red-algae. PE in cyanobacteria stays less studied so far as compared to ...that in red algae. In this study, PE from marine cyanobacteria Halomicronema sp. R31DM is purified and subjected for its structural characterisation by X-ray crystallography in order to understand its light-harvesting characteristics. The crystal structure is solved to a resolution-limit of 2.21 Å with reasonable R-factors values, 0.16/0.21 (R
work
/ R
free
). PE forms hexamer of hetero-dimers made up of two peptide chains, α- and β-subunits containing 2 and 3 phycoerythrobilin (PEB) chromophores covalently attached to them, respectively. Geometry of five chromophores is analysed along with their relative position within the PE hexamer. Also, their interactions with the surrounding microenvironment are analysed. The plausible energy transfer pathways in hexamer structure have been predicted based on relative position and geometry of chromophores. This structure enriches the structural information of cyanobacterial PE in order to understand its light-harvesting capacity.
Communicated by Ramaswamy H. Sarma
This study aims to identify the role of subjective factors (age, sex, and comorbidities) and procedure-specific factors (aspiration volume) in influencing the yield of progenitor cells in bone marrow ...aspiration concentrate (BMAC) harvested from the iliac crest. A retrospective analysis was conducted on 58 patients (male:female = 31:27; mean age: 52.56 ± 18.14 years) who underwent BMAC therapy between January 2020 and June 2021. The factors analyzed include individual factors such as age, sex, and comorbid conditions, and procedural factors such as aspirate volume. The mononuclear cell (MNC) count and colony-forming unit (CFU) assay were used to assess the yield of progenitors in the aspirate. Pearson's correlation test was performed for the age, aspirate volume, and outcome parameters, such as MNC and CFU. We used the chi-square test to analyze the role of sex and comorbidities on cellular yield. The mean volume of aspirate used for BMAC therapy was 66.65 (±17.82) mL. The mean MNC count of the BMAC was 19.94 (±16.34) × 10
cells, which formed 11 (±12) CFUs. Evidence of statistically significant positive associations was noted between the CFUs developed from the BMAC and the MNC count within them (r = 0.95,
< 0.001). The sex of the individual did not play any significant role in MNC count (
= 0.092) or CFUs formed (
= 0.448). The age of the individual showed evidence of a statistically significant negative association with the MNC count (r = -0.681,
< 0.001) and CFUs (r = -0.693,
< 0.001), as did the aspiration volume with the MNC count (r = -0.740,
< 0.001) and CFUs (r = -0.629,
< 0.001). We also noted a significant reduction in the MNC count (
= 0.002) and CFUs formed (
= 0.004) when the patients presented comorbidities. Individual factors such as age, comorbid conditions, and procedure factors such as aspirate volume significantly affected the yield of progenitor cells in the BMAC. The sex of the individual did not influence the yield of progenitor cells in BMAC.
Type Ia supernova Hubble residuals have been shown to correlate with host galaxy mass, imposing a major obstacle for their use in measuring dark energy properties. Here, we calibrate the fundamental ...metallicity relation (FMR) of Mannucci et al. for host mass and star formation rates measured from broadband colors alone. We apply the FMR to the large number of hosts from the SDSS-II sample of Gupta et al. and find that the scatter in the Hubble residuals is significantly reduced when compared with using only stellar mass (or the mass-metallicity relation) as a fit parameter. Our calibration of the FMR is restricted to only star-forming galaxies and in the Hubble residual calculation we include only hosts with log(SFR) > - 2. Our results strongly suggest that metallicity is the underlying source of the correlation between Hubble residuals and host galaxy mass. Since the FMR is nearly constant between z = 2 and the present, use of the FMR along with light-curve width and color should provide a robust distance measurement method that minimizes systematic errors.
Bariatric surgery is proven to change eating behavior and cause sustained weight loss, yet the exact mechanisms underlying these changes are not clearly understood. We explore this in a novel way by ...examining how bariatric surgery affects the brain-gut-microbiome (BGM) axis.
Patient demographics, serum, stool, eating behavior questionnaires, and brain magnetic resonance imaging (MRI) were collected before and 6 months after laparoscopic sleeve gastrectomy (LSG). Differences in eating behavior and brain morphology and resting-state functional connectivity in core reward regions were correlated with serum metabolite and 16S microbiome data.
LSG resulted in significant weight loss and improvement in maladaptive eating behaviors as measured by the Yale Food Addiction Scale (YFAS). Brain imaging showed a significant increase in brain volume of the putamen (
.adj < 0.05) and amygdala (
.adj < 0.05) after surgery. Resting-state connectivity between the precuneus and the putamen was significantly reduced after LSG (
.adj = 0.046). This change was associated with YFAS symptom count.
,
, and
were associated with reduced connectivity between these areas. Metabolomic profiles showed a positive correlation between this brain connection and a phosphatidylcholine metabolite.
Bariatric surgery modulates brain networks that affect eating behavior, potentially through effects on the gut microbiota and its metabolites.
We consider the vehicle routing problem with stochastic demands (VRPSD). We give randomized approximation algorithms achieving approximation guarantees of 1 + α for split-delivery VRPSD, and 2 + α ...for unsplit-delivery VRPSD; here α is the best approximation guarantee for the traveling salesman problem. These bounds match the best known for even the respective deterministic problems Altinkemer, K., B. Gavish. 1987. Heuristics for unequal weight delivery problems with a fixed error guarantee. Oper. Res. Lett. 6(4) 149-158; Altinkemer, K., B. Gavish. 1990. Heuristics for delivery problems with constant error guarantees. Transportation Res. 24(4) 294-297. We also show that the "cyclic heuristic" for split-delivery VRPSD achieves a constant approximation ratio, as conjectured in Bertsimas Bertsimas, D. J. 1992. A vehicle routing problem with stochastic demand. Oper. Res. 40(3) 574-585. PUBLICATION ABSTRACT
Despite recent advances, there is still a major need to better understand the interactions between brain function and chronic gut inflammation and its clinical implications. Alterations in executive ...function have previously been identified in several chronic inflammatory conditions, including inflammatory bowel diseases. Inflammation-associated brain alterations can be captured by connectome analysis. Here, we used the resting-state fMRI data from 222 participants comprising three groups (ulcerative colitis (UC), irritable bowel syndrome (IBS), and healthy controls (HC), N = 74 each) to investigate the alterations in functional brain wiring and cortical stability in UC compared to the two control groups and identify possible correlations of these alterations with clinical parameters. Globally, UC participants showed increased functional connectivity and decreased modularity compared to IBS and HC groups. Regionally, UC showed decreased eigenvector centrality in the executive control network (UC < IBS < HC) and increased eigenvector centrality in the visual network (UC > IBS > HC). UC also showed increased connectivity in dorsal attention, somatomotor network, and visual networks, and these enhanced subnetwork connectivities were able to distinguish UC participants from HCs and IBS with high accuracy. Dynamic functional connectome analysis revealed that UC showed enhanced cortical stability in the medial prefrontal cortex (mPFC), which correlated with severe depression and anxiety-related measures. None of the observed brain changes were correlated with disease duration. Together, these findings are consistent with compromised functioning of networks involved in executive function and sensory integration in UC.
Gaucher disease (GD) is an autosomal recessive inherited lysosomal storage disease that often presents in early childhood and is associated with damage to multiple organ systems. Many challenges ...associated with GD diagnosis and management arise from the considerable heterogeneity of disease presentations and natural history. Phenotypic classification has traditionally been based on the absence (in type 1 GD) or presence (in types 2 and 3 GD) of neurological involvement of varying severity. However, patient management and prediction of prognosis may be best served by a dynamic, evolving definition of individual phenotype rather than by a rigid system of classification. Patients may experience considerable delays in diagnosis, which can potentially be reduced by effective screening programs; however, program implementation can involve ethical and practical challenges. Variation in the clinical course of GD and an uncertain prognosis also complicate decisions concerning treatment initiation, with differing stakeholder perspectives around efficacy and acceptable cost/benefit ratio. We review the challenges faced by physicians in the diagnosis and management of GD in pediatric patients. We also consider future directions and goals, including acceleration of accurate diagnosis, improvements in the understanding of disease heterogeneity (natural history, response to treatment, and prognosis), the need for new treatments to address unmet needs for all forms of GD, and refinement of the tools for monitoring disease progression and treatment efficacy, such as specific biomarkers.
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