Mesenchymal Stromal Cell Delivery Via Cardiopulmonary Bypass Provides Neuroprotection in a Juvenile Porcine Model.

Oxidative/inflammatory stresses due to cardiopulmonary bypass (CPB) cause prolonged microglia activation and cortical dysmaturation, thereby contributing to neurodevelopmental impairments in children with congenital heart disease (CHD). This study found that delivery of mesenchymal stromal cells (MSCs) via CPB minimizes microglial activation and neuronal apoptosis, with subsequent improvement of cortical dysmaturation and behavioral alteration after neonatal cardiac surgery. Furthermore, transcriptomic analyses suggest that exosome-derived miRNAs may be the key drivers of suppressed apoptosis and STAT3-mediated microglial activation. Our findings demonstrate that MSC treatment during cardiac surgery has significant translational potential for improving cortical dysmaturation and neurological impairment in children with CHD.

Low cost centrifugal melt spinning for distributed manufacturing of non-woven media.

Centralized manufacturing and global supply chains have emerged as an efficient strategy for large-scale production of goods throughout the 20th century. However, while this system of production is highly efficient, it is not resilient. The COVID-19 pandemic has seen numerous supply chains fail to adapt to sudden changes in supply and demand, including those for goods critical to the pandemic response such as personal protective equipment. Here, we consider the production of the non-woven polypropylene filtration media used in face filtering respirators (FFRs). The FFR supply chain's reliance on non-woven media sourced from large, centralized manufacturing facilities led to a supply chain failure. In this study, we present an alternative manufacturing strategy that allows us to move towards a more distributed manufacturing practice that is both scalable and robust. Specifically, we demonstrate that a fiber production technique known as centrifugal melt spinning can be implemented with modified, commercially-available cotton candy machines to produce nano- and microscale non-woven fibers. We evaluate several post processing strategies to transform the produced material into viable filtration media and then characterize these materials by measuring filtration efficiency and breathability, comparing them against equivalent materials used in commercially-available FFRs. Additionally, we demonstrate that waste plastic can be processed with this technique, enabling the development of distributed recycling strategies to address the growing plastic waste crisis. Since this method can be employed at small scales, it allows for the development of an adaptable and rapidly deployable distributed manufacturing network for non-woven materials that is financially accessible to more people than is currently possible.

Sorting of proteins with shape and curvature anisotropy on a lipid bilayer tube.

Curvature induced sorting of lipid membrane bound proteins has been widely studied through experiments that induce curvature variation in a giant unilamellar lipid-bilayer vesicle with adsorbed proteins by pulling thin cylindrical tethers. In the theoretical space, this has been supplemented with models that capture curvature dependent interaction between membrane and idealized protein particles, through free energy contributions. Many membrane proteins such as the BAR domain proteins are known to have extremely anisotropic shapes and soft interacting potentials, whereas the idealizations of protein particles explored in models have only assumed them as hard disk-like particles with curvature anisotropy. Here, we present a model of sorting of the proteins while including the effects of softness in their interaction potentials, shape anisotropy in the protein structure, and curvature anisotropy in the interactions with the membrane. This is based on a clean separation of free energy contributions from non-ideal fluid behavior of soft anisotropic particles and curvature interactions between proteins and membranes. We probe the behavior of the sorting function under limiting conditions and show that it converges to the previously derived models. In addition to this, we present a comparison of the variation in sorting ratio due to the observed variation in the shape parameter values in known membrane proteins. Finally, using published experimental data for membrane proteins, we perform fitting and derive model parameters. We observe that shape anisotropy adversely affects the sorting of proteins to a high curvature region, whereas curvature anisotropy and softer interaction between proteins favor sorting.

Advances in Diagnostic Imaging in Pediatric Gastroenterology.

PURPOSE OF REVIEW: The purpose is to provide a review of cross-sectional imaging updates in the assessment of gastrointestinal diseases, relevant to clinical practice and research. RECENT FINDINGS: New magnetic resonance imaging contrast agents (Eovist) are taken up by hepatocytes and excreted via the biliary tree. As such, a lesion will retain contrast only if hepatocytes are present, which aids in refining the differential diagnosis. Magnetic resonance enterography is a method for non-invasively diagnosing and following various GI conditions, predominantly inflammatory bowel disease. Contrast-enhanced ultrasound uses gas-filled microbubbles providing superb temporal resolution most notably in the arterial phase, which aids in differentiating lesions. Elastography is a new technique which assesses stiffness of liver for evaluating fibrosis. These new techniques provide more accurate diagnoses and information, often limiting ionizing radiation exposure from other modalities. While ultrasound will still remain the initial imaging modality, familiarity with these other options is valuable for appropriate pathology workup.

Iatrogenic immunodeficiency-associated lymphoproliferative disorder in a child with B-cell acute lymphoblastic leukemia.

Iatrogenic immunodeficiency-associated lymphoproliferative disorders (LPDs) are a group of lymphoid proliferations or lymphomas that are well known to be associated with an immunosuppressed state. These disorders most commonly occur following hematopoietic or solid organ transplantation (called post-transplant lymphoproliferative disorders or PTLD), but cases have also been described during the treatment of autoimmune and rheumatologic disorders by immunosuppressive and immunomodulatory medications. These disorders are strongly associated with infection by the Epstein-Barr virus (EBV) as a result of impaired immune function in the immunosuppressed state. While this phenomenon has been well documented in autoimmune conditions, cases affecting pediatric patients while on anti-leukemia chemotherapy are lacking. In this report, we describe a case of a pediatric immunosuppressed patient with recurrent sinusitis found to have a nasopharyngeal mass consistent with EBV-positive B-cell lymphoproliferative disorder resembling a polymorphic PTLD during the maintenance phase of B-cell Acute Lymphoblastic Leukemia (ALL) therapy. The patient was successfully treated with rituximab without any cytotoxic chemotherapy, highlighting the importance of recognizing this clinical entity in non-transplant patients with hematologic malignancies.

Retrospective comparison of the Low Risk Ankle Rules and the Ottawa Ankle Rules in a pediatric population.

BACKGROUND: A recent multicenter prospective Canadian study presented prospective evidence supporting the Low Risk Ankle Rules (LRAR) as a means of reducing the number of ankle radiographs ordered for children presenting with an ankle injury while maintaining nearly 100% sensitivity. This is in contrast to a previous prospective study which showed that this rule yielded only 87% sensitivity. OBJECTIVE: It is important to further investigate the LRAR and compare them with the already validated Ottawa Ankle Rules (OAR) to potentially curb healthcare costs and decrease unnecessary radiation exposure without compromising diagnostic accuracy. METHODS: We conducted a retrospective chart review of 980 qualifying patients ages 12months to 18years presenting with ankle injury to a commonly staffed 310 bed children's hospital and auxiliary site pediatric emergency department. RESULTS: There were 28 high-risk fractures identified. The Ottawa Ankle Rules had a sensitivity of 100% (95% CI 87.7-100), specificity of 33.1% (95% CI 30.1-36.2), and would have reduced the number of ankle radiographs ordered by 32.1%. The Low Risk Ankle Rules had a sensitivity of 85.7% (95% CI 85.7-96), specificity of 64.9% (95% CI 61.8-68), and would have reduced the number of ankle radiographs ordered by 63.1%. The latter rule missed 4 high-risk fractures. CONCLUSION: The Low Risk Ankle Rules may not be sensitive enough for use in Pediatric Emergency Departments, while the Ottawa Ankle Rules again demonstrated 100% sensitivity. Further research on ways to implement the Ottawa Ankle Rules and maximize its ability to decrease wait times, healthcare costs, and improve patient satisfaction are needed.

Software-based PET-MR image coregistration: combined PET-MRI for the rest of us!

BACKGROUND: With the introduction of hybrid positron emission tomography/magnetic resonance imaging (PET/MRI), a new imaging option to acquire multimodality images with complementary anatomical and functional information has become available. Compared with hybrid PET/computed tomography (CT), hybrid PET/MRI is capable of providing superior anatomical detail while removing the radiation exposure associated with CT. The early adoption of hybrid PET/MRI, however, has been limited. OBJECTIVE: To provide a viable alternative to the hybrid PET/MRI hardware by validating a software-based solution for PET-MR image coregistration. MATERIALS AND METHODS: A fully automated, graphics processing unit-accelerated 3-D deformable image registration technique was used to align PET (acquired as PET/CT) and MR image pairs of 17 patients (age range: 10 months-21 years, mean: 10 years) who underwent PET/CT and body MRI (chest, abdomen or pelvis), which were performed within a 28-day (mean: 10.5 days) interval. MRI data for most of these cases included single-station post-contrast axial T1-weighted images. Following registration, maximum standardized uptake value (SUVmax) values observed in coregistered PET (cPET) and the original PET were compared for 82 volumes of interest. In addition, we calculated the target registration error as a measure of the quality of image coregistration, and evaluated the algorithm's performance in the context of interexpert variability. RESULTS: The coregistration execution time averaged 97±45 s. The overall relative SUVmax difference was 7% between cPET-MRI and PET/CT. The average target registration error was 10.7±6.6 mm, which compared favorably with the typical voxel size (diagonal distance) of 8.0 mm (typical resolution: 0.66 mm × 0.66 mm × 8 mm) for MRI and 6.1 mm (typical resolution: 3.65 mm × 3.65 mm × 3.27 mm) for PET. The variability in landmark identification did not show statistically significant differences between the algorithm and a typical expert. CONCLUSION: We have presented a software-based solution that achieves the many benefits of hybrid PET/MRI scanners without actually needing one. The method proved to be accurate and potentially clinically useful.

Supratentorial primitive neuroectodermal tumor metastasis to the abdomen via a ventriculoperitoneal shunt.

Primitive neuroectodermal tumors (PNETs) include a heterogeneous group that originate from primitive neuroepithelial cells. PNETs are prone to cerebrospinal fluid seeding and central nervous system spread. Infratentorial PNET, or medulloblastoma, is a common brain tumor in children and metastatic spread to the abdomen via a ventriculoperitoneal (VP) shunt has been described. Supratentorial PNETs are much less common. We present a rare case of a predominantly supratentorial PNET metastasizing to the abdomen via a VP shunt and discuss the radiological findings. This case demonstrates the small but real risk of metastatic spread, which should be weighed when considering VP shunt placement.

Multiple-stress tolerance of ionizing radiation-resistant bacterial isolates obtained from various habitats: correlation between stresses.

Isolation of five ionizing radiation (IR)-resistant bacteria by screening of isolates from various habitats classified as common and stressed is reported. IR-resistant isolates exhibited varying degrees of resistance to gamma-radiation and were classified as highly and moderately radiation resistant. Resistance to ultraviolet (UV) radiation correlated well with gamma-radiation resistance, whereas a comparable desiccation resistance for all the highly and moderately radiation-resistant isolates was observed. However, salt tolerance failed to correlate with IR resistance, indicating a divergent evolution of the salt tolerance and radiation resistance. Characterization of isolates by the amplified rDNA restriction analysis profiling attested to the clustering of these isolates with their stress phenotype. 16S rRNA gene-based analysis of the isolates showed that the bacteria with similar-resistance physiologies clustered together and belonged to related genera. Hydrogen peroxide resistance and mitomycin survival patterns of the isolates indicated the roles of oxidative-stress tolerance in desiccation survival and recombination repair in higher radiation resistance, respectively.

Formulation of medium constituents by multiresponse analysis of central composite design to enhance chitinase production in Pantoea dispersa.

In the present study, a high chitinase producing strain Pantoea dispersa was isolated from the sea dumps at Bhavnagar, India. Chitin, urea, CaCl2 and MgSO4 x 7H2O were variables used in central composite design for chitinase production. Chitinase, biomass and pH were the responses used in different models to evaluate individually fit ones. Quadratic model was found to be fit for chitinase response whereas in the case of biomass and pH, linear model was found to be fit without the effect of others. Chitinase production was optimized with respect to other responses such as biomass and pH in multiresponse analysis of response surface design by using desirability approach. In multiresponse analysis, following medium formulation (g/l), chitin, 15; urea, 0.32; CaCl2, 0.10 and MgSO4 x 7H2O, 0.08 was found to predict optimum chitinase production of 482.77 units/ml with overall highest desirability of 0.854 as compared to other formulations. The selection of model was done on the basis of high Adjusted R-squared value and lowered p-value for each model in individual analysis of each response. In multiresponse experiment, it was found that for response chitinase quadratic model and for responses pH and biomass linear models were well fit. Through desirability analysis, it was found that in the chitinase production, pH was essential as compared to biomass in P. dispersa. Endochitinase and chitobiase actvities were also studied.

Isolation and identification of marine chitinolytic bacteria and their potential in antifungal biocontrol.

Chitinolytic marine bacterial strains (30) were isolated from the sea dumps at Bhavnagar, India. They were screened as chitinase producers on the basis of zone of clearance on chitin agar plates incorporated with calcofluor white M2R for the better resolution. Out of these, three strains namely, Pseudomonas sp., Pantoea dispersa and Enterobacter amnigenus showed high chitinase production. They were also found to produce proteases and therefore have a good potential for use as antifungal biocontrol agents for the control of fungal plant pathogens. These strains could degrade and utilize the mycelia of Macrophomina phaseoliena (Tassi) Goidanich and Fusarium sp. In vitro, these strains could inhibit the growth of Fusarium sp. and M. phaseolina. The culture filtrate inhibiting hyphal elongation was observed microscopically.

Purification and characterization of chitinase from Alcaligenes xylosoxydans.

Extracellular chitinase from Alcaligenes xylosoxydans was purified to electrophoretic homogeneity using affinity and gel filtration chromatography. The molecular mass of chitinase was estimated to be 45 kDa and 44 kDa by SDS-PAGE and gel-filtration, respectively. The enzyme was optimally active at 50 degrees C (over 30 min) and pH 5. Activity staining after PAGE showed a single band. The Km for chitin was 3 g l-1. Cu2+ and Na+ at 5 mM inhibited chitinase activity to 25% while Ca2+, Mg2+ and Ba2+ had no effect at the same concentration. The purified enzyme degraded mycelia of Aspergillus niger.

Cerebral and systemic hemodynamics changes during upright tilt in chronic fatigue syndrome.

BACKGROUND AND PURPOSE: During head-up tilt (HUT), patients with chronic fatigue syndrome (CFS) have higher rates of neurally mediated hypotension (NMH) and postural tachycardia syndrome (POTS) than healthy controls. The authors studied whether patients with CFS were also more likely to have abnormal cerebral blood flow velocity (CBFV) compared with controls in response to orthostatic stress. METHODS: Transcranial Doppler monitoring of middle cerebral artery (MCA) CBFV was performed during 3-stage HUT prospectively in 26 patients with CFS and 23 healthy controls. At the same time, continuous monitoring of arterial blood pressure (BP), heart rate (HR), endtidal CO2 (ET-CO2) were performed. Results are reported as mean +/- SD. RESULTS: NMH developed in 21 patients with CFS and in 14 controls (P = .22). POTS was present in 9 CFS patients and 7 controls (P = .76). Supine HR was higher in CFS patients, but all other hemodynamics and CBFV measures were similar at baseline. The median time to hypotension did not differ, but the median time to onset of orthostatic symptoms was shorter in those with CFS (P < .001). The CBFV did not differ between groups in the supine posture, at 1 or 5 minutes after upright tilt, at 5 or 1 minute before the end of the test, or at termination of the test. Mean CBFV fell at termination of tilt testing in those with CFS and controls. ET-CO2 was lower at termination of the test in those with CFS versus controls (P = .002). CONCLUSIONS: The results of this study are not consistent with the hypothesis that patients with CFS have a distinctive pattern of MCA CBFV changes in response to orthostatic stress.

Estimation of gallbladder ejection fraction utilizing cholecystokinin-stimulated magnetic resonance cholangiography and comparison with hepatobiliary scintigraphy.

PURPOSE: To evaluate the utility of magnetic resonance cholangiography (MRC) in estimation of gallbladder ejection fraction (GBEF) and to comparing this value to the conventional method, hepatobiliary scintigraphy (HBS). MATERIALS AND METHODS: Twenty-one healthy volunteers were imaged on sequential weeks to determine GBEF using MRC and HBS. GBEF was calculated by HBS after infusion of 20 ng/kg of sincalide following injection of 111 Mbq of Tc 99(m) mebrofenin. For estimation by MRC, imaging of the gallbladder was performed before and after slow infusion of sincalide every 5 minutes, for a total of 60 minutes. Gallbladder imaging was performed using a heavily T2-weighted 2D fast spin echo (FSE) sequence. Data was analyzed using a variance component analysis technique. RESULTS: Mean GBEF by HBS was 65.7%, with an SD of +/-27.3%. Mean GBEF by MRC was 62.7%, with an SD of +/- 20.4%. If minimum normal GBEF is set at 35%, two of the cases showed discordance, with HBS calculating an abnormally low average GBEF compared to MRC. Additionally, two cases showed abnormally low GBEF for both modalities. The coefficient of correlation between HBS and MRC was 0.72. Inter- and intraobserver variance is acceptable within the two modalities with <1.1% variation. CONCLUSION: GBEF can be calculated with MRC, yielding similar values when a group of volunteers are considered. Further study with symptomatic patients is needed to determine the validity of this technique for clinical diagnosis.