Substrate Micropatterning as a New in Vitro Cell Culture System to Study Myelination

Artículo de publicación ISIMyelination is a highly regulated developmental process whereby oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system ensheathe axons with a multilayered concentric membrane. Axonal myelination increases the velocity of nerve impulse propagation. In this work, we present a novel in vitro system for coculturing primary dorsal root ganglia neurons along with myelinating cells on a highly restrictive and micropatterned substrate. In this new coculture system, neurons survive for several weeks, extending long axons on defined Matrigel tracks. On these axons, myelinating cells can achieve robust myelination, as demonstrated by the distribution of compact myelin and nodal markers. Under these conditions, neurites and associated myelinating cells are easily accessible for studies on the mechanisms of myelin formation and on the effects of axonal damage on the myelin sheath.Regenerative Medicine and Nanomedicine Initiative of the Canadian Institutes of Health Research (CIHR) RMF-7028 FONDECYT 1080252 CIHR Ministry of Industry of Canada Rio Tinto Alcan Molson Foundatio

Development and validation of a unifying pre-treatment decision tool for intracranial and extracranial metastasis-directed radiotherapy

BackgroundThough metastasis-directed therapy (MDT) has the potential to improve overall survival (OS), appropriate patient selection remains challenging. We aimed to develop a model predictive of OS to refine patient selection for clinical trials and MDT.Patients and methodsWe assembled a multi-institutional cohort of patients treated with MDT (stereotactic body radiation therapy, radiosurgery, and whole brain radiation therapy). Candidate variables for recursive partitioning analysis were selected per prior studies: ECOG performance status, time from primary diagnosis, number of additional non-target organ systems involved (NOS), and intracranial metastases.ResultsA database of 1,362 patients was assembled with 424 intracranial, 352 lung, and 607 spinal treatments (n=1,383). Treatments were split into training (TC) (70%, n=968) and internal validation (IVC) (30%, n=415) cohorts. The TC had median ECOG of 0 (interquartile range [IQR]: 0-1), NOS of 1 (IQR: 0-1), and OS of 18 months (IQR: 7-35). The resulting model components and weights were: ECOG = 0, 1, and > 1 (0, 1, and 2); 0, 1, and > 1 NOS (0, 1, and 2); and intracranial target (2), with lower scores indicating more favorable OS. The model demonstrated high concordance in the TC (0.72) and IVC (0.72). The score also demonstrated high concordance for each target site (spine, brain, and lung).ConclusionThis pre-treatment decision tool represents a unifying model for both intracranial and extracranial disease and identifies patients with the longest survival after MDT who may benefit most from aggressive local therapy. Carefully selected patients may benefit from MDT even in the presence of intracranial disease, and this model may help guide patient selection for MDT

Rapid and Long-Lasting Increase in Sites for Synapse Assembly during Late-Phase Potentiation in Rat Hippocampal Neurons

Long-term potentiation in hippocampal neurons has stages that correspond to the stages of learning and memory. Early-phase (10–30 min) potentiation is accompanied by rapid increases in clusters or puncta of presynaptic and postsynaptic proteins, which depend on actin polymerization but not on protein synthesis. We have now examined changes in pre- and postsynaptic puncta and structures during glutamate-induced late-phase (3 hr) potentiation in cultured hippocampal neurons. We find that (1) the potentiation is accompanied by long-lasting maintenance of the increases in puncta, which depends on protein synthesis, (2) most of the puncta and synaptic structures are very dynamic, continually assembling and disassembling at sites that are more stable than the puncta or structures themselves, (3) the increase in presynaptic puncta appears to be due to both rapid and more gradual increases in the number of sites where the puncta may form, and also to the stabilization of existing puncta, (4) under control conditions, puncta of postsynaptic proteins behave similarly to puncta of presynaptic proteins and share sites with them, and (5) the increase in presynaptic puncta is accompanied by a similar increase in presumably presynaptic structures, which may form at distinct as well as shared sites. The new sites could contribute to the transition between the early and late phase mechanisms of plasticity by serving as seeds for the formation and maintenance of new synapses, thus acting as local “tags” for protein synthesis-dependent synaptic growth during late-phase plasticity

Validation of clinical acceptability of deep-learning-based automated segmentation of organs-at-risk for head-and-neck radiotherapy treatment planning

IntroductionOrgan-at-risk segmentation for head and neck cancer radiation therapy is a complex and time-consuming process (requiring up to 42 individual structure, and may delay start of treatment or even limit access to function-preserving care. Feasibility of using a deep learning (DL) based autosegmentation model to reduce contouring time without compromising contour accuracy is assessed through a blinded randomized trial of radiation oncologists (ROs) using retrospective, de-identified patient data.MethodsTwo head and neck expert ROs used dedicated time to create gold standard (GS) contours on computed tomography (CT) images. 445 CTs were used to train a custom 3D U-Net DL model covering 42 organs-at-risk, with an additional 20 CTs were held out for the randomized trial. For each held-out patient dataset, one of the eight participant ROs was randomly allocated to review and revise the contours produced by the DL model, while another reviewed contours produced by a medical dosimetry assistant (MDA), both blinded to their origin. Time required for MDAs and ROs to contour was recorded, and the unrevised DL contours, as well as the RO-revised contours by the MDAs and DL model were compared to the GS for that patient.ResultsMean time for initial MDA contouring was 2.3 hours (range 1.6-3.8 hours) and RO-revision took 1.1 hours (range, 0.4-4.4 hours), compared to 0.7 hours (range 0.1-2.0 hours) for the RO-revisions to DL contours. Total time reduced by 76% (95%-Confidence Interval: 65%-88%) and RO-revision time reduced by 35% (95%-CI,-39%-91%). All geometric and dosimetric metrics computed, agreement with GS was equivalent or significantly greater (p<0.05) for RO-revised DL contours compared to the RO-revised MDA contours, including volumetric Dice similarity coefficient (VDSC), surface DSC, added path length, and the 95%-Hausdorff distance. 32 OARs (76%) had mean VDSC greater than 0.8 for the RO-revised DL contours, compared to 20 (48%) for RO-revised MDA contours, and 34 (81%) for the unrevised DL OARs.ConclusionDL autosegmentation demonstrated significant time-savings for organ-at-risk contouring while improving agreement with the institutional GS, indicating comparable accuracy of DL model. Integration into the clinical practice with a prospective evaluation is currently underway

Late rectal anastomotic leakage treated with diode laser FiLaC probe. A case report of a new minimal invasive treatment

Introduction: Anastomotic Leakage (AL) is one of the most important early postoperative complication of the adenocarcinoma's surgical treatment. Fistula Laser Closure (FiLaC®) is a minimal invasive technique that use diode laser energy to obtain the fistula track obliteration and it is finding large application for other affection characterized by fistula tracts presence. Presentation of case: A 56 years old male, with no clinical history of adenocarcinoma in his family, underwent a laparoscopic low anterior resection with ileostomy for a rectal adenocarcinoma. Approximately 3 months after the procedure an anastomotic leak with an associated abscess was found. The patient underwent an endoscopic FiLaC off-label procedure on the AL and after further 4 months, he obtained a complete resolution of the anastomosis dehiscence. Discussion: The literature is poor about the minimal invasive AL treatment and there is no paper about the management of the AL with the FiLaC® procedure. For asymptomatic patients a conservative solution is preferred, it could be considered a drain positioning for emptying abscesses and for irrigation or the use of an Endosponge to decrease the resolution time. The FiLaC® procedure could be a more feasible technique that could also reduce the healing time as well with no discomfort for the patient. Conclusion: Considering the results and our patient healing time, we think that an off-label application of FiLaC® procedure on asymptomatic low anastomotic leak could be an opportunity for a morbidity resolution shorter than the simple wait and see strategy, and more sustainable for the patient

Prophylactic sublay non-absorbable mesh positioning following midline laparotomy in a clean-contaminated field: randomized clinical trial (PROMETHEUS)

Background: Incisional hernia is a frequent postoperative complication after midline laparotomy. Prophylactic mesh augmentation in abdominal wall closure after elective surgery is recommended, but its role in emergency surgery is less well defined. Methods: This prospective randomized trial evaluated the incidence of incisional hernia in patients undergoing urgent midline laparotomy for clean-contaminated surgery. Closure using a slowly absorbable running suture was compared with closure using an additional sublay mesh (Parietex ProGrip™). Patients were randomized just before abdominal wall closure using computer-generated permuted blocks. Patients, care providers, staff collecting data, and those assessing the endpoints were all blinded to the group allocation. Patients were followed up for 24 months by means of clinical and ultrasonographic evaluations. Results: From January 2015 to June 2018, 200 patients were randomized: 100 to primary closure (control group) and 100 to Parietex ProGrip™ mesh-supported closure (mesh group). Eight patients in the control group and six in the mesh group were lost to follow-up. By 24 months after surgery, 21 patients in the control group and six in the mesh group had developed incisional hernia (P = 0.002). There was no difference between groups in the incidence of haematoma (2 versus 5; P = 0.248) and superficial wound infection (4 versus 5; P = 0.733). Multivariable analysis confirmed the role of mesh in preventing incisional hernia (odds ratio 0.11, 95 per cent c.i. 0.03 to 0.37; P < 0.001). One patient in the mesh group required mesh removal because of deep infection. Conclusion: Prophylactic mesh-augmented abdominal wall closure after urgent laparotomy in clean-contaminated wounds is safe and effective in reducing the incidence of incisional hernia. Registration number: NCT04436887 (http://www.clinicaltrials.gov). Graphical abstract: An RCT was conducted to compare the widely recommended midline laparotomy closure using a slowly absorbable running suture with closure using a sublay mesh (Parietex ProGrip™), in patients undergoing urgent midline laparotomy for clean-contaminated surgery. Patients were followed up for 24 months with clinical and ultrasonographic evaluation during outpatient visits. Prophylactic reinforcement of the midline abdominal wall, using a ProGrip™ Parietex mesh in the retromuscular position, at the time of urgent laparotomy in clean-contaminated wounds was safe and effective in reducing the incidence of incisional hernia, although larger studies with longer follow-up are required

1/f1∕f noise in gold nanoparticle chemosensors

We present a systematic study of low-frequency noise in Au nanoparticle chemosensors. All the sensors we have studied exhibit 1/f1∕f-type noise at low frequencies. The magnitude of the 1/f1∕f noise was smaller in devices with a larger device area, indicating that the 1/f1∕f noise is caused by intrinsic processes. The noise amplitude was found to be strongly temperature dependent between 40–300 K40–300K, with a local peak at around 100 K100K, and weakly dependent below 40 K40K. The noise data could not be fit by a single activated process indicating that multiple noise processes must be present in our sensors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87853/2/073506_1.pd

IPOM plus versus IPOM standard in incisional hernia repair: results of a prospective multicenter trial

PurposeLaparoscopic ventral hernia repair is a well-established technique with satisfying outcomes even at long term for the treatment of incisional and ventral hernia. However, the literature debate is still ongoing regarding the preferred surgical technique. Nowadays, two approaches are commonly adopted: the intraperitoneal onlay mesh repair (sIPOM) and the intraperitoneal onlay mesh reinforcement with defect closure before mesh placement (pIPOM). The aim of this prospective analysis is to compare the postoperative outcomes of patients treated for incisional hernia (IH) with sIPOM and pIPOM after 36 months follow-up in terms of recurrence, quality of life and wound events.MethodsPatients receiving pIPOM and sIPOM for IH were actively followed up for 36 months. At the outpatient clinic, hernia recurrence (HR), mesh bulging (MB), quality of life with the Gastrointestinal Quality of Life Index (GIQLI) and wound events were assessed.ResultsBetween January 2015 and January 2019, 98 patients underwent a pIPOM and 89 underwent an sIPOM. At 36 months, nine patients (4 in pIPOM and 5 in sIPOM) experienced an HR, while MB was recorded in four patients in pIPOM and nine in sIPOM. No statistically significant difference could be identified also in terms of final GIQLI score and wound events.ConclusionsLVHR with or without fascial closure, also in our study, provides satisfactory results in terms of safety and efficacy. The discordant results in the literature are probably related to independent variables such as the type of mesh, the type of suture and closure technique. Therefore, was the funeral of sIPOM done too early?Study dataset is available on ClinicalTrials.gov IDNCT0571221