Gene expression and growth factor analysis in early nerve regeneration following segmental nerve defect reconstruction with a mesenchymal stromal cell-enhanced decellularized nerve all

Background: The purpose of this study was to evaluate the molecular mechanisms underlying nerve repair by a decellularized nerve allograft seeded with adiposederived mesenchymal stromal cells (MSCs) and compare it to the unseeded allograft and autograft nerve. Methods: Undifferentiated MSCs were seeded onto decellularized nerve allografts and used to reconstruct a 10 mm gap in a rat sciatic nerve model. Gene expression profiles of genes essential for nerve regeneration and immunohistochemical staining (IHC) for PGP9.5, NGF, RECA-1, and S100 were obtained 2 weeks postoperatively. Results: Semi-quantitative RT-PCR analysis showed that the angiogenic molecule VEGFA was significantly increased in seeded allografts, and transcription factor SOX2 was downregulated in seeded allografts. Seeded grafts showed a significant increase in immunohistochemical markers NGF and RECA-1, when compared with unseeded allografts. Conclusions: MSCs contributed to the secretion of trophic factors. A beneficial effect of the MSCs on angiogenesis was found when compared with the unseeded nerve allograft, but implanted MSCs did not show evidence of differentiation into Schwann cell-like cells

Automatic correction of dental artifacts in PET/MRI

A challenge when using current magnetic resonance (MR)-based attenuation correction in positron emission tomography/MR imaging (PET/MRI) is that the MRIs can have a signal void around the dental fillings that is segmented as artificial air-regions in the attenuation map. For artifacts connected to the background, we propose an extension to an existing active contour algorithm to delineate the outer contour using the nonattenuation corrected PET image and the original attenuation map. We propose a combination of two different methods for differentiating the artifacts within the body from the anatomical air-regions by first using a template of artifact regions, and second, representing the artifact regions with a combination of active shape models and k-nearest-neighbors. The accuracy of the combined method has been evaluated using 25 [Formula: see text]-fluorodeoxyglucose PET/MR patients. Results showed that the approach was able to correct an average of [Formula: see text] of the artifact areas

Understanding Iodine Chemistry Over the Northern and Equatorial Indian Ocean

Observations of halogen oxides, ozone, meteorological parameters, and physical and biogeochemical water column measurements were made in the Indian Ocean and its marine boundary layer as a part of the Second International Indian Ocean Expedition (IIOE-2). The expedition took place on board the oceanographic research vessel Sagar Nidhi during 4–22 December 2015 from Goa, India, to Port Louis, Mauritius. Observations of mixed layer depth, averaged temperature, salinity, and nitrate concentrations were used to calculate predicted iodide concentrations in the seawater. The inorganic iodine ocean-atmosphere flux (hypoiodous acid [HOI] and molecular iodine [I2]) was computed using the predicted iodide concentrations, measured atmospheric ozone, and wind speed. Iodine oxide (IO) mixing ratios peaked at 0.47 ± 0.29 pptv (parts per trillion by volume) in the remote open ocean environment. The estimated iodide concentrations and HOI and I2 fluxes peaked at 200/500 nM, 410/680 nmol·m−2·day−1, and 20/80 nmol·m−2·day−1, respectively, depending on the parameterization used. The calculated fluxes for HOI and I2 were higher closer to the Indian subcontinent; however, atmospheric IO was only observed above the detection limit in the remote open ocean environment. We use NO2 observations to show that titration of IO by NO2 is the main reason for this result. These observations show that inorganic iodine fluxes and atmospheric IO show similar trends in the Indian Ocean marine boundary layer, but the impact of inorganic iodine emissions on iodine chemistry is buffered in elevated NOx environments, even though the estimated oceanic iodine fluxes are higher

Dental artifacts in the head and neck region::implications for Dixon-based attenuation correction in PET/MR

BACKGROUND: In the absence of CT or traditional transmission sources in combined clinical positron emission tomography/magnetic resonance (PET/MR) systems, MR images are used for MR-based attenuation correction (MR-AC). The susceptibility effects due to metal implants challenge MR-AC in the neck region of patients with dental implants. The purpose of this study was to assess the frequency and magnitude of subsequent PET image distortions following MR-AC. METHODS: A total of 148 PET/MR patients with clear visual signal voids on the attenuation map in the dental region were included in this study. Patients were injected with [(18)F]-FDG, [(11)C]-PiB, [(18)F]-FET, or [(64)Cu]-DOTATATE. The PET/MR data were acquired over a single-bed position of 25.8 cm covering the head and neck. MR-AC was based on either standard MR-AC(DIXON) or MR-AC(INPAINTED) where the susceptibility-induced signal voids were substituted with soft tissue information. Our inpainting algorithm delineates the outer contour of signal voids breaching the anatomical volume using the non-attenuation-corrected PET image and classifies the inner air regions based on an aligned template of likely dental artifact areas. The reconstructed PET images were evaluated visually and quantitatively using regions of interests in reference regions. The volume of the artifacts and the computed relative differences in mean and max standardized uptake value (SUV) between the two PET images are reported. RESULTS: The MR-based volume of the susceptibility-induced signal voids on the MR-AC attenuation maps was between 1.6 and 520.8 mL. The corresponding/resulting bias of the reconstructed tracer distribution was localized mainly in the area of the signal void. The mean and maximum SUVs averaged across all patients increased after inpainting by 52% (± 11%) and 28% (± 11%), respectively, in the corrected region. SUV underestimation decreased with the distance to the signal void and correlated with the volume of the susceptibility artifact on the MR-AC attenuation map. CONCLUSIONS: Metallic dental work may cause severe MR signal voids. The resulting PET/MR artifacts may exceed the actual volume of the dental fillings. The subsequent bias in PET is severe in regions in and near the signal voids and may affect the conspicuity of lesions in the mandibular region. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40658-015-0112-5) contains supplementary material, which is available to authorized users

Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial

Background Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery

Stenting the ureteroneocystostomy reduces urological complications in kidney transplantation: a noninferiority randomized controlled trial, SPLINT trial

The role of ureteral stents in living-donor kidney transplantation remains uncertain. In this randomized controlled trial (SPLINT), we compared urological complications in living-donor kidney transplantations performed with or without stents. We included 200 consecutive patients that received living-donor kidney transplantations at the Erasmus MC, University Medical Center, Rotterdam. Patients (124 males, 76 females, mean age 54 ± 13) were randomized for suprapubic externalized single J stents (N = 100) or no stent (N = 100). The primary outcome was the probability of a percutaneous nephrostomy insertion (PCN) during a 12-month follow-up. To assess whether no stenting is noninferior to stenting, we allowed the probability of a PCN to increase by at most 5% (this is the noninferiority margin). Baseline characteristics were comparable between groups. In the no-stent group, there were more PCN insertions, 14% (95% CI 4.3–23.7%); urinary leakages, 12% (95% CI 5.4–21.3%); and surgical re-interventions because of urological complications, 8% (95% CI 1.5–14.5%). The stent group had more hematuria, 26% (95% CI 13.1–38.9%); and graft rejections, 15% (95% CI 2.7–27.3%). Patients in both groups had similar mean GFRs at several time points. Besides a better Euro-Qol-5D in the no-stent group at 2 and 6 weeks postoperative, similar quality of life was reported based on SF-36 and Euro-Qol-5D scores. In this trial, noninferiority has not been demonstrated for no-stent placement in relation to the number urological complications

Subclinical thyroid dysfunction and cognitive decline in old age

&lt;p&gt;Background: Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).&lt;/p&gt; &lt;p&gt;Methods: Prospective longitudinal study of men and women aged 70–82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) &#60;0.45 mU/L or &#62;4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests.&lt;/p&gt; &lt;p&gt;Results: Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up.&lt;/p&gt; &lt;p&gt;Conclusion: We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.&lt;/p&gt

Simultaneous hyperpolarized 13C-pyruvate MRI and 18F-FDG-PET in cancer (hyperPET):feasibility of a new imaging concept using a clinical PET/MRI scanner

In this paper we demonstrate, for the first time, the feasibility of a new imaging concept - combined hyperpolarized (13)C-pyruvate magnetic resonance spectroscopic imaging (MRSI) and (18)F-FDG-PET imaging. This procedure was performed in a clinical PET/MRI scanner with a canine cancer patient. We have named this concept hyper PET. Intravenous injection of the hyperpolarized (13)C-pyruvate results in an increase of (13)C-lactate, (13)C-alanine and (13)C-CO(2) ((13)C-HCO(3)) resonance peaks relative to the tissue, disease and the metabolic state probed. Accordingly, with dynamic nuclear polarization (DNP) and use of (13)C-pyruvate it is now possible to directly study the Warburg Effect through the rate of conversion of (13)C-pyruvate to (13)C-lactate. In this study, we combined it with (18)F-FDG-PET that studies uptake of glucose in the cells. A canine cancer patient with a histology verified local recurrence of a liposarcoma on the right forepaw was imaged using a combined PET/MR clinical scanner. PET was performed as a single-bed, 10 min acquisition, 107 min post injection of 310 MBq (18)F-FDG. (13)C-chemical shift imaging (CSI) was performed just after FDG-PET and 30 s post injection of 23 mL hyperpolarized (13)C-pyruvate. Peak heights of (13)C-pyruvate and (13)C-lactate were quantified using a general linear model. Anatomic (1)H-MRI included axial and coronal T1 vibe, coronal T2-tse and axial T1-tse with fat saturation following gadolinium injection. In the tumor we found clearly increased (13)C-lactate production, which also corresponded to high (18)F-FDG uptake on PET. This is in agreement with the fact that glycolysis and production of lactate are increased in tumor cells compared to normal cells. Yet, most interestingly, also in the muscle of the forepaw of the dog high (18)F-FDG uptake was observed. This was due to activity in these muscles prior to anesthesia, which was not accompanied by a similarly high (13)C-lactate production. Accordingly, this clearly demonstrates how the Warburg Effect directly can be demonstrated by hyperpolarized (13)C-pyruvate MRSI. This was not possible with (18)F-FDG-PET imaging due to inability to discriminate between causes of increased glucose uptake. We propose that this new concept of simultaneous hyperpolarized (13)C-pyruvate MRSI and PET may be highly valuable for image-based non-invasive phenotyping of tumors. This methods may be useful for treatment planning and therapy monitoring