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The absence of published reference values for multilayer-specific strain measurement using cardiac magnetic resonance (CMR) in young healthy individuals limits its use. This study aimed to establish normal global and layer-specific strain values in healthy children and young adults using a deformable registration algorithm (DRA). A retrospective study included 131 healthy children and young adults (62 males and 69 females) with a mean age of 16.6 ± 3.9 years. CMR examinations were conducted using 1.5T scanners, and strain analysis was performed using TrufiStrain research prototype software (Siemens Healthineers, Erlangen, Germany). Global and layer-specific strain parameters were extracted from balanced Steady-state free precession cine images. Statistical analyses were conducted to evaluate the impact of demographic variables on strain measurements. The peak global longitudinal strain (LS) was −16.0 ± 3.0%, peak global radial strain (RS) was 29.9 ± 6.3%, and peak global circumferential strain (CS) was −17.0 ± 1.8%. Global LS differed significantly between males and females. Transmural strain analysis showed a consistent pattern of decreasing LS and CS from endocardium to epicardium, while radial strain increased. Basal-to-apical strain distribution exhibited decreasing LS and increasing CS in both global and layer-specific analysis. This study uses DRA to provide reference values for global and layer-specific strain in healthy children and young adults. The study highlights the impact of sex and age on LS and body mass index on RS. These insights are vital for future cardiac assessments in children, particularly for early detection of heart diseases. [ABSTRACT FROM AUTHOR]

Few level I trauma, tertiary care, academic centers have a paid, permanent reading room coordinator (RRC) to facilitate image management services during off-hour calls, to minimize interruptions to reading workflow. The purpose of this study is to investigate the effect of an RRC on the efficiency of radiology residents signing preliminary reports for emergency department (ED) and inpatient studies. A pre- and postintervention retrospective review was performed, using carestream PACS to retrieve imaging studies read on call during two time periods—July 1 to December 1, 2019 (pre-RRC), and July 1 to December 1, 2021 (post-RRC). Efficiency of residents signing preliminary reports was measured by turnaround time (TAT), defined as the time from when a study was marked complete by a technologist to when a preliminary report was signed by a resident, in PACS. In the above time periods, residents interpreted a total of 64,406 studies on call. For ED studies, the mean TAT was 7.0 min shorter post-RRC, compared with pre-RRC (95% confidence interval [CI]: –7.8 to –6.1, (t = 15.50, degrees of freedom (df) = 31,866, P <.0001). The percentage of ED studies signed within 30 min increased from 57.7% to 65.8%, an increase of 8.1% (95% CI: 7.0% to 9.1%) after employing an RRC (χ2 = 228.11, df = 1, P <.0001). For inpatient studies, the mean TAT was 10.2 min shorter post-RRC (95% CI: –12.3 to –8.0, t = 9.22, df = 25,193, P <.0001). An RRC increased radiology resident on-call workflow efficiency, facilitating care for patients in both the ED and inpatient setting. [Display omitted] [ABSTRACT FROM AUTHOR]

Cardiac magnetic resonance imaging is crucial for diagnosing cardiovascular diseases, but lengthy postprocessing and manual segmentation can lead to observer bias. Deep learning (DL) has been proposed for automated cardiac segmentation; however, its effectiveness is limited by the slice range selection from base to apex. In this study, we integrated an automated slice range classification step to identify basal to apical short-axis slices before DL-based segmentation. We employed publicly available Multi-Disease, Multi-View & Multi-Center Right Ventricular Segmentation in Cardiac MRI data set with short-axis cine data from 160 training, 40 validation, and 160 testing cases. Three classification and seven segmentation DL models were studied. The top-performing segmentation model was assessed with and without the classification model. Model validation to compare automated and manual segmentation was performed using Dice score and Hausdorff distance and clinical indices (correlation score and Bland-Altman plots). The combined classification (CBAM-integrated 2D-CNN) and segmentation model (2D-UNet with dilated convolution block) demonstrated superior performance, achieving Dice scores of 0.952 for left ventricle (LV), 0.933 for right ventricle (RV), and 0.875 for myocardium, compared to the stand-alone segmentation model (0.949 for LV, 0.925 for RV, and 0.867 for myocardium). Combined classification and segmentation model showed high correlation (0.92-0.99) with manual segmentation for biventricular volumes, ejection fraction, and myocardial mass. The mean absolute difference (2.8-8.3 mL) for clinical parameters between automated and manual segmentation was within the interobserver variability range, indicating comparable performance to manual annotation. Integrating an initial automated slice range classification step into the segmentation process improves the performance of DL-based cardiac chamber segmentation. [ABSTRACT FROM AUTHOR]

The degree of chordee associated with hypospadias impacts operative management. Unfortunately, poor inter-observer reliability in assessing chordee by multiple methods in vitro has been demonstrated. This variability may be related to the fact that chordee is not a discrete angle, but rather an arc-like curvature similar to that of a banana. On an attempt to improve this variability, we assessed the inter-rater reliability of a novel method of chordee measurement and compared it to measurements with a goniometer both in vitro and in vivo. In vitro assessment of curvature was performed using 5 bananas. In vivo chordee measurement was performed during 43 hypospadias repairs. On in vitro and in vivo cases, chordee was assessed independently by faculty and resident physicians. Angle assessment was performed in a standard manner with a goniometer and with a smartphone app using ruler measurements of the length and width of the arc (Summary Figure). The proximal and distal aspect of the arc to be measured was marked on the bananas, whereas the penile measurements were taken from the penoscrotal to the sub-coronal junctions. In vitro banana assessment demonstrated strong intra- and inter-rater reliability for length (0.89 and 0.88, respectively) and width measurements (0.97 and 0.96). The calculated angle demonstrated an intra- and inter-rater reliability of 0.67 and 0.67. The banana goniometer/protractor measurements were weak with an intra-rater and inter-rater reliability of 0.33 and 0.21. With hypospadias chordee, the inter-rater reliability was strong for length and width measurements (0.95 and 0.94) and 0.48 for calculated angle. The inter-rater reliability of the goniometer angle was 0.96. Further assessment of inter-rater goniometer reliability was performed relative to degree of chordee as characterized by faculty. The inter-rater reliability for ≤15°, 16–30, and ≥30° was 0.68 (n = 20), 0.34 (n = 14), and 0.90 (n = 9), respectively. When the goniometer angle was classified as ≤15, 16–30, or ≥30° by one physician, it was classified outside of this range by the other physician 23%, 47%, and 25% of the time, respectively. Our data demonstrate significant limitations of the goniometer for assessing chordee in vitro and in vivo. We were unable to demonstrate significant improvement in chordee assessment using arc length and width measurements to calculate radians. Reliable and precise techniques for measuring hypospadias chordee remain elusive and draw into question the validity and usability of management algorithms employing discrete values. [Display omitted] [ABSTRACT FROM AUTHOR]

To investigate the role of participant level of effort (LoE) on outcome in post-acute brain injury rehabilitation with the hypothesis that greater effort is associated with more positive outcomes. Observational cohort study. Comprehensive integrated rehabilitation program for brain injury within a skilled nursing facility. Consecutive admissions with acquired brain injury (N=101). Individualized interdisciplinary brain injury rehabilitation; therapist rating of participant LoE with Acquired Brain Injury LoE Scale (ABI-LoES) during physical therapy, occupational therapy, and speech and language pathology sessions. Mayo-Portland Adaptability Inventory, fourth edition (MPAI-4); Supervision Rating Scale (SRS). Linear regression showed that discharge MPAI-4 Total T scores were significantly associated with mean ABI-LoES rating, admission MPAI-4 Total T scores, age at admission, and days from injury but not with standard deviation of ABI-LoES rating, sex, injury type, length of stay, or treatment before or during the COVID-19 pandemic. Discharge SRS scores were significantly associated with mean ABI-LoES rating, admission SRS scores, and age. A 1-unit increase in mean ABI-LoES rating was associated with 5.1-unit lower discharge MPAI-4 Total T scores and 1.5 lower discharge SRS scores, after controlling for other variables. Logistic regression showed that the odds of achieving a minimal clinically important difference on the MPAI-4 were 8.34 times higher with each 1-unit increase in mean ABI-LoES rating after controlling for other variables. Admission MPAI-4 was negatively associated with mean ABI-LoES rating (β=−0.07, t =−8.85, P <.0001). After controlling for nonmodifiable variables, average ABI-LoES rating is positively associated with outcome. Initial level of disability is negatively associated with mean ABI-LoES rating. [ABSTRACT FROM AUTHOR]

Background: Oral administration of purified omega-3 (ω-3) PUFAs is associated with changes to the fecal microbiome. However, it is not known whether this effect is associated with increased PUFA concentrations in the gut.Objectives: We investigated the luminal bioavailability of oral ω-3 PUFAs (daily dose 1 g EPA and 1g DHA free fatty acid equivalents as triglycerides in soft-gel capsules, twice daily) and changes to the gut microbiome, in the ileum.Methods: Ileostomy fluid (IF) and blood were obtained at baseline, after first capsule dosing (median 2 h), and at a similar time after final dosing on day 28, in 11 individuals (median age 63 y) with a temporary ileostomy. Fatty acids were measured by LC-tandem MS. The ileal microbiome was characterized by 16S rRNA PCR and Illumina sequencing.Results: There was a mean 6.0 ± 9.8-fold and 6.6 ± 9.6-fold increase in ileal EPA and DHA concentrations (primary outcome), respectively, at 28 d, which was associated with increased RBC ω-3 PUFA content (P ≤ 0.05). The first oral dose did not increase the ileal ω-3 PUFA concentration except in 4 individuals, who displayed high luminal EPA and DHA concentrations, which reduced to concentrations similar to the overall study population at day 28, suggesting physiological adaptation. Bacteroides, Clostridium, and Streptococcus were abundant bacterial genera in the ileum. Ileal microbiome variability over time and between individuals was large, with no consistent change associated with acute ω-3 PUFA dosing. However, high concentrations of EPA and DHA in IF on day 28 were associated with higher abundance of Bacteroides (r2 > 0.86, P < 0.05) and reduced abundance of other genera, including Actinomyces (r2 > 0.94, P < 0.05).Conclusions: Oral administration of ω-3 PUFAs leads to increased luminal ω-3 PUFA concentrations and changes to the microbiome, in the ileum of individuals with a temporary ileostomy. This study is registered on the ISRCTN registry as ISRCTN14530452. [ABSTRACT FROM AUTHOR]

Recently a report by Ruan et al. in Nature described how relatively simple random heteropolymers can replicate the properties of biological fluids. These polymers capture the segmental-level interactions between proteins and could enhance folding of membrane proteins, improve stability, and enable DNA sequestration in a chemistry specific manner. [ABSTRACT FROM AUTHOR]

Significant parallels exist between the phase separation behavior of polymers in solution and the types of biomolecular condensates, or 'membraneless organelles,' that are of increasing interest in living systems. Liquid–liquid phase separation allows for compartmentalization and the sequestration of materials and can be harnessed as a sensitive strategy for responding to small changes in the environment. Here, I review many of the parallels and synergies between ongoing efforts to study and take advantage of phase separation in living versus synthetic materials. Image 1 • Compartmentalization and reaction control can be achieved by phase separation. • Phase separation allows for dramatic response to a signal or environmental trigger. • Parallels exist between phase-separated materials in living and in synthetic systems. • The liquid versus solid nature of the phase-separated material is dictated by the strength of the interactions. • Material design is complicated by the diversity of possible interaction motifs. [ABSTRACT FROM AUTHOR]

Ionotropic glutamate receptors (GluRs) are targets for modulation in Hebbian and homeostatic synaptic plasticity and are remodeled by development, experience, and disease. We have probed the impact of synaptic glutamate levels on the two postsynaptic GluR subtypes at the Drosophila neuromuscular junction, GluRA and GluRB. We first demonstrate that GluRA and GluRB compete to establish postsynaptic receptive fields, and that proper GluR abundance and composition can be orchestrated in the absence of any synaptic glutamate release. However, excess glutamate adaptively tunes postsynaptic GluR abundance, echoing GluR scaling observed in mammalian systems. Furthermore, when GluRA vs. GluRB competition is eliminated, GluRB becomes insensitive to glutamate modulation. In contrast, GluRA is now homeostatically regulated by excess glutamate to maintain stable miniature activity, where Ca2+ permeability through GluRA receptors is required. Thus, excess glutamate, GluR competition, and Ca2+ signaling collaborate to selectively target GluR subtypes for homeostatic regulation at postsynaptic compartments. [Display omitted] • Glutamate receptor subtypes compete to establish postsynaptic receptive fields • Excess glutamate release triggers adaptive receptor scaling • GluRA receptors are selectively targeted for homeostatic scaling in Drosophila • Homeostatic receptor scaling requires calcium permeability through GluRA Differences in glutamate receptor abundance and composition underlie numerous forms of synaptic plasticity, but how receptors respond to changes in glutamate itself is unclear. Han et al. demonstrate that excess glutamate release provokes subtype-specific, homeostatic receptor downscaling. Calcium permeability through the glutamate receptor is necessary for homeostatic regulation. [ABSTRACT FROM AUTHOR]

Highlights • 3D spheroids are more resistant to Hypericin-PDT than 2D cell models. • ABCG2 is upregulated in 3D spheroids as compared to 2D cell models. • Inhibiting ABCG2 could potentially improve response to Hypericin-PDT. Abstract Background Photodynamic Therapy (PDT) is an attractive modality for treating solid cancers. This study evaluates the efficacy of Hypericin-PDT as a cytotoxic therapy in colorectal cancer (CRC), using 2D cell cultures and 3D multicellular tumour spheroids. Methods Spheroids were generated through forced-floating and agitation-based techniques. 2D and spheroid models of HT29 and HCT116 CRC cells were incubated with Hypericin (0–200 nM) for 16 h. Cultures were irradiated with light (1 J/cm2) and cytotoxicity assessed using Propidium Iodide fluorescence. Expression of ABCG2 protein was assessed by immunoassays in 2D and spheroid cultures. The effect of ABCG2 inhibition, using 10 μM Ko143, on cytotoxicity following Hypericin-PDT was evaluated. Results Hypericin-PDT produced a significant reduction in HT29 (p < 0.0001) and HCT116 (p < 0.0001) cell viability in 2D cultures, with negligible non-phototoxicity. Spheroids were more resistant than 2D cultures to Hypericin-PDT (HT29: p = 0.003, HCT116: p = 0.006) and had a greater expression of ABCG2. Inhibition of ABCG2 in spheroids with Ko143 resulted in an enhanced Hypericin-PDT effect compared to Hypericin-PDT alone (HT29: p = 0.04, HCT116: p = 0.01). Conclusions Hypericin-PDT has reduced efficacy in CRC spheroids as compared to 2D cultures, which may be attributable through upregulation in ABCG2. The clinical efficacy of Hypericin-PDT may be enhanced by ABCG2 inhibition. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether diurnal variation in cough reflex sensitivity exists in healthy young adults when a tidal-breathing method is used. Fifty-three participants (19–37 years) underwent cough reflex testing on two occasions: once in the morning (between 9 am – midday) and once in the afternoon (between 2–5 pm). The order of testing was counter-balanced. Within each assessment, participants inhaled successively higher citric acid concentrations via a facemask, with saline solution randomly interspersed to control for a placebo response. The lowest concentration that elicited a reflexive cough response was recorded. Morning cough thresholds (mean = 0.6 mol/L) were not different from afternoon cough thresholds (mean = 0.6 mol/L), p = 0.16, T = 101, r = −0.14. We found no evidence of diurnal variability in cough reflex testing. There was, however, an order effect irrespective of time of day, confirming that healthy participants are able to volitionally modulate their cough response. [ABSTRACT FROM AUTHOR]

Summary Histone deacetylases (HDACs) have been extensively studied as drug targets in neurodegenerative diseases, but less is known about their role in healthy neurons. We tested zinc-dependent HDACs using RNAi in Drosophila melanogaster and found memory deficits with RPD3 and HDAC6 . We demonstrate that HDAC6 is required in both the larval and adult stages for normal olfactory memory retention. Neuronal expression of HDAC6 rescued memory deficits, and we demonstrate that the N-terminal deacetylase (DAC) domain is required for this ability. This suggests that deacetylation of synaptic targets associated with the first DAC domain, such as the active-zone scaffold Bruchpilot, is required for memory retention. Finally, electrophysiological experiments at the neuromuscular junction reveal that HDAC6 mutants exhibit a partial block of homeostatic plasticity, suggesting that HDAC6 may be required for the stabilization of synaptic strength. The learning deficit we observe in HDAC6 mutants could be a behavioral consequence of these synaptic defects. [ABSTRACT FROM AUTHOR]

Abstract: This paper reports a method for fabricating multilayer microfluidic protein crystallization platforms using different materials to achieve X-ray transparency and compatibility with crystallization reagents. To validate this approach, three soluble proteins, lysozyme, thaumatin, and ribonuclease A were crystallized on-chip, followed by on-chip diffraction data collection. We also report a chip with an array of wells for screening different conditions that consume a minimal amount of protein solution as compared to traditional screening methods. A large number of high quality isomorphous protein crystals can be grown in the wells, after which slices of X-ray data can be collected from many crystals still residing within the wells. Complete protein structures can be obtained by merging these slices of data followed by further processing with crystallography software. This approach of using an X-ray transparent chip for screening, crystal growth, and X-ray data collection enables room temperature data collection from many crystals mounted in parallel, which thus eliminates crystal handling and minimizes radiation damage to the crystals. [Copyright &y& Elsevier]

The CO 2 receptor in mosquitoes is broadly tuned to detect many diverse odorants. The receptor consists of three subunits (Gr1, Gr2, and Gr3) in mosquitoes but only two subunits in Drosophila : Gr21a (Gr1 ortholog) and Gr63a (Gr3 ortholog). We demonstrate that Gr21a is required for CO 2 responses in Drosophila, as has been shown for Gr63a. Next, we generate a Drosophila double mutant for Gr21a and Gr63a , and in this background, we functionally express combinations of Aedes Gr1 , Gr2 , and Gr3 genes in the CO 2 empty neuron. Only two subunits, Gr2 and Gr3, suffice for response to CO 2. Addition of Gr1 increases sensitivity to CO 2 , whereas it decreases the response to pyridine. The inhibitory effect of the antagonist isobutyric acid is observed upon addition of Gr1. Gr1 therefore increases the diversity of ligands of the receptor and modulates the response of the receptor complex. • The Gr21a subunit of the heteromeric CO 2 receptor is needed to detect CO 2 in Drosophila • Aedes Gr2 and Gr3 together detect CO 2 and pyridine • Addition of Gr1 increases sensitivity to CO 2 and decreases sensitivity to pyridine • Addition of Gr1 allows inhibition by isobutyric acid Kumar et al. analyze contributions of the conserved subunits of the insect CO 2 receptor to detection of diverse odor classes in an empty neuron system. They demonstrate that only two of the three subunits are required for CO 2 detection in mosquitoes, while the third subunit modulates responses of both CO 2 and non-CO 2 ligands. [ABSTRACT FROM AUTHOR]

The complex relationship between kinetics and substrate morphology during enzymatic depolymerization of melt processed poly(ethylene terephthalate) (PET) is explored and the effects of competing transformations are analyzed. Extruded PET substrates from post-consumer recycled PET (RPET) bottles flakes subjected to enzymatic depolymerization are examined to reveal increases in crystallinity from ∼10% post-extrusion to > 30% after 3 days of depolymerization as well as increases in glass transition temperature (T g) from ∼66 °C to > 80 °C. Further investigation into this behavior shows that post-extrusion RPET substrates do not exhibit changes in crystallinity when subjected to dry annealing at 65 °C in an oven over 7 days, but they do experience annealing in depolymerization buffer solution with no enzymes at 65 °C within 3 days. This difference may be attributed to plasticization of PET in the presence of water, also known as solvent induced crystallization. The impact of this plasticized annealing behavior is demonstrated by subjecting RPET substrates to increasing enzyme-to-substrate loads. As enzyme load increases, overall conversion of substrates increases despite crystallinity also increasing to similar levels regardless of the initial enzyme loading. The competition between depolymerization and crystallization suggests that the rate at which PET substrates are depolymerized at the operational temperature is integral to achieving high conversion to monomeric product. This, in turn, also suggests that savings from lowered enzyme loadings may be more detrimental than helpful in pursuing the most cost-effective recycling systems. [Display omitted] • Recrystallization of PET in water competes with enzymatic depolymerization. • PET recrystallization can be overcome by increased enzyme concentration. • Depolymerization is slow below T g , but no recrystallization occurs. [ABSTRACT FROM AUTHOR]

Cis -regulatory elements (CREs) play a critical role in the development and disease-states of all human cell types. In the retina, CREs have been implicated in several inherited disorders. To better characterize human retinal CREs, we performed single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) and single-nucleus RNA sequencing (snRNA-seq) on the developing and adult human retina and on induced pluripotent stem cell (iPSC)-derived retinal organoids. These analyses identified developmentally dynamic, cell-class-specific CREs, enriched transcription-factor-binding motifs, and putative target genes. CREs in the retina and organoids are highly correlated at the single-cell level, and this supports the use of organoids as a model for studying disease-associated CREs. As a proof of concept, we disrupted a disease-associated CRE at 5q14.3, confirming its principal target gene as the miR-9-2 primary transcript and demonstrating its role in neurogenesis and gene regulation in mature glia. This study provides a resource for characterizing human retinal CREs and showcases organoids as a model to study the function of CREs that influence development and disease. [Display omitted] • Single-cell atlas of cis -regulatory elements in developing and adult human retina • Correlation of DNA accessibility between human retina and retinal organoids • Association of disease-risk loci with cell-class-specific accessibility • Modeling of enhancer function at the 5q14.3 retinal disease-risk locus Thomas et al. generate atlases of cis -regulatory elements in the developing and mature human retina and organoids through the use of snATAC-seq and snRNA-seq. The authors compare these systems in order to benchmark the potential of organoids for investigating retinal enhancers and show that a highly conserved, disease-associated enhancer at 5q14.3 regulates retinal development through miR9-2. [ABSTRACT FROM AUTHOR]

Abstract: Aim of the study: Validated molecular biomarkers are urgently required in colon cancer (CC) to accurately define prognosis and, ideally, to predict response to therapeutic modalities such as adjuvant chemotherapy. We aimed to identify and characterise a novel membrane-associated protein in CC tissues which may offer diagnostic and, potentially, therapeutic targeting opportunities. Methods: Label-free mass spectrometric (MS) quantitation was employed to profile matched colon tissues for malignancy-associated proteins. The putative diagnostic utility of a chosen marker was evaluated using immunohistochemistry (IHC) on 367 CC tissue samples contained within the NCI Progression Colon Cancer tissue microarray (TMA) set. Results: Retinoic acid-induced protein 3 (RAI3) was initially identified as a plasma membrane protein overexpressed in CC. Cancer-associated RAI3 over-expression was confirmed by RAI3 IHC. Although RAI3 IHC expression patterns were variable within neoplastic epithelium, 76% (n =236) of interpretable CC cases (n =312) displayed diffuse cytoplasmic expression. Of note, a sub-set of CC tissues (n =23, 7.4%) displayed very strong cytoplasmic expression, a feature significantly associated with disease recurrence in Dukes’ A–C (stage I–III) patients (hazard ratio (HR)=3.076, [95%confidence interval (CI)=1.738–5.445]; p <0.001) when compared to low or negative expression of RAI3. This association retained univariate significance in Dukes’ B/stage II patients only (HR=3.494, [95%CI=1.197–10.20]; p <0.022). Significantly, the prognostic capacity of RAI3 was maintained in the stage I–III cohort following multivariate modelling (HR=2.11, [95%CI 1.109–4.017], p =0.023). Conclusion: RAI3 is a putative prognostic marker that identifies a small subset of CC patients with high recurrence risk. This study demonstrates the potential value of modern proteomic technology in clinically relevant applications. [Copyright &y& Elsevier]

Abstract: Background: High mobility group box-1 (HMGB-1), a recently identified inflammatory cytokine, is implicated in the pathogenesis of several inflammatory, infective and neoplastic processes. Patterns of expression following blunt trauma have not been adequately reported in the literature. This study aimed to quantify the serum concentrations of HMGB-1 following blunt trauma, and assess its relationship with the more established interleukin 6 (IL-6). Patients and methods: 20 patients with median injury severity score 17 (range 9–36) sustaining closed diaphyseal fractures of the femur treated by intramedullary nailing were included in the study. Serum concentrations of HMGB-1 and IL-6 were measured at several time points during their treatment. Results: A strong correlation was observed between admission and day 1 post-op concentrations of IL-6 and both the injury severity score (ISS) and the requirement for intensive care unit treatment. Serum concentrations of HMGB-1 did not demonstrate such a correlation. Around day 3 when IL-6 concentrations begin to fall, serum HMGB-1 concentrations were observed to increase. Conclusions: IL-6 concentration measured early after admission is again shown to be strongly associated with overall injury severity and requirement for intensive care unit treatment. In contrast, HMGB-1 appears to be a late inflammatory mediator with levels becoming elevated once serum concentrations of IL-6 begin to fall. However, we were unable to demonstrate any relationship with injury severity or requirement for ICU care at any stage. These preliminary findings may form the basis for future research in this area. [Copyright &y& Elsevier]

Abstract: The aim of this study was to investigate whether growth factors essential for fracture healing are substantially increased in the immediate aftermath following reaming of the intramedullary cavity for stabilisation of femoral shaft fractures. Consecutive adult patients whose femoral shaft fractures stabilised with either reamed (10 patients) or unreamed (10 patients) intramedullary nailing were studied. Peripheral blood samples and samples from the femoral canal before and after reaming and nail insertion were collected. Serum was extracted and using Elisa colorimetric assays the concentration of Platelet Derived Growth Factor-ΒΒ (PDGF), Vascular Endothelial Growth Factor (VEGF), Insulin-like Growth Factor-I (IGF-I), Transforming Growth Factor beta 1 (TGF-β1) and Bone Morphogenetic Protein-2 (BMP-2) was measured. The mean age of the twenty patients who participated in the study was 38 years (range 20–63). Reaming substantially increased all studied growth factors (p <0.05) locally in the femoral canal. VEGF and PDGF were increased after reaming by 111.2% and 115.6% respectively. IGF-I was increased by 31.5% and TGF-β1 was increased by 54.2%. In the unreamed group the levels of PDGF-BB, VEGF, TGF-β1 remained unchanged while the levels of IGF-I decreased by 10%. The levels of these mediators in the peripheral circulation were not altered irrespectively of the nail insertion technique used. BMP-2 levels during all time points were below the detection limit of the immunoassay. This study indicates that reaming of the intramedullary cavity is associated with increased liberation of growth factors. The osteogenic effect of reaming could be secondary not only to grafting debris but also to the increased liberation of these molecules. [Copyright &y& Elsevier]