MNK2 deficiency potentiates ß-cell regeneration via translational regulation.

Regenerating pancreatic ß-cells is a potential curative approach for diabetes. We previously identified the small molecule CID661578 as a potent inducer of ß-cell regeneration, but its target and mechanism of action have remained unknown. We now screened 257 million yeast clones and determined that CID661578 targets MAP kinase-interacting serine/threonine kinase 2 (MNK2), an interaction we genetically validated in vivo. CID661578 increased ß-cell neogenesis from ductal cells in zebrafish, neonatal pig islet aggregates and human pancreatic ductal organoids. Mechanistically, we found that CID661578 boosts protein synthesis and regeneration by blocking MNK2 from binding eIF4G in the translation initiation complex at the mRNA cap. Unexpectedly, this blocking activity augmented eIF4E phosphorylation depending on MNK1 and bolstered the interaction between eIF4E and eIF4G, which is necessary for both hypertranslation and ß-cell regeneration. Taken together, our findings demonstrate a targetable role of MNK2-controlled translation in ß-cell regeneration, a role that warrants further investigation in diabetes.

Real-time management of intra-hospital patient transport requests.

This paper addresses the management of patients' transportation requests within a hospital, a very challenging problem where requests must be scheduled among the available porters so that patients arrive at their destination timely and the resources invested in patient transport are kept as low as possible. Transportation requests arrive during the day in an unpredictable manner, so they need to be scheduled in real-time. To ensure that the requests are scheduled in the best possible manner, one should also reconsider the decisions made on pending requests that have not yet been completed, a process that will be referred to as rescheduling. This paper proposes several policies to trigger and execute the rescheduling of pending requests and three approaches (a mathematical formulation, a constructive heuristic, and a local search heuristic) to solve each rescheduling problem. A simulation tool is proposed to assess the performance of the rescheduling strategies and the proposed scheduling methods to tackle instances inspired by a real mid-size hospital. Compared to a heuristic that mimics the way requests are currently handled in our partner hospital, the best combination of scheduling method and rescheduling strategy produces an average 5.7 minutes reduction in response time and a 13% reduction in the percentage of late requests. Furthermore, since the total distance walked by porters is substantially reduced, our experiments demonstrate that it is possible to reduce the number of porters - and therefore the operating costs - without reducing the current level of service.

Exploring parenthood in first episode of psychosis: the potential role of the offspring in the outcome of women.

PURPOSE: The study aimed to explore the role of parenthood at first episode of psychosis (FEP) on recovery, with a focus on potential sex differences. METHODS: Sociodemographic, clinical, and neurocognitive information was considered on 610 FEP patients form the PAFIP cohort (Spain). Baseline and three-year follow-up comparisons were carried out. Chi-square tests and ANCOVA analysis were performed controlling for the effect of age and years of education. RESULTS: Men comprised 57.54% of the sample, with only 5.41% having offspring when compared to 36.29% of women. Parenthood was related to shorter duration of untreated illness (DUI) in women with children (12.08 months mothers vs. 27.61 months no mothers), showing mothers better premorbid adjustment as well. Childless men presented the worst premorbid adjustment and the highest cannabis and tobacco consumption rates. Mothers presented better global cognitive function, particularly in attention, motor dexterity and executive function at three-year follow-up. CONCLUSIONS: Diminished parental rates among FEP men could be suggested as a consequence of a younger age of illness onset. Sex roles in caregiving may explain the potential role of parenthood on premorbid phase, with a better and heathier profile, and a more favorable long-term outcome in women. These characteristics may be relevant when adjusting treatment specific needs in men and women with and without offspring.

Portal hypertension has no role in perioperative bleeding during liver transplantation with systematic porto-caval shunt.

BACKGROUND: More than a half of patients undergoing liver transplantation (LT) receive intraoperative transfusion. Portal hypertension (PHT) may contribute to perioperative blood loss. We study the relationship between preoperative hepatic venous pressure gradient (HVPG) values and intraoperative transfusion requirements in adult patients undergoing LT. METHODS: 160 cirrhotic patients undergoing first elective LT (2009-2019) with an HVPG measurement within the previous 6 months were included. Surgical technique was piggyback with portocaval shunt (PCS). The association of HVPG and other variables with transfusion requirements and blood loss were studied. RESULTS: Blood loss (ml/kg) was positively correlated with HVPG, among other variables, but at multivariable analysis it only remained associated with MELD-Na and HCC indication. Regarding RBC transfusion, MELD-Na and hemoglobin were independently associated with the need and magnitude of RBC transfusion. Subanalysis by surgical stage (hepatectomy, anhepatic, neohepatic) and by serial HVPG cut-offs found no clear associations with either bleeding or transfusion. DISCUSSION: The severity of PHT plays a minor role on bleeding and transfusion during LT in a contemporary cohort with systematic PCS. Main determinants of transfusion are liver function and baseline hemoglobin, which would seem the suitable goal to optimize transfusion in LT.

Endoscopy-Related Bleeding and Thromboembolic Events in Patients on Direct Oral Anticoagulants or Vitamin K Antagonists.

BACKGROUND & AIMS: Few prospective studies have assessed the safety of direct oral anticoagulants (DOACs) in elective endoscopy. Our primary aim was to compare the risks of endoscopy-related gastrointestinal bleeding and thromboembolic events in patients on DOACs or vitamin K antagonists (VKAs) in this setting. Secondarily, we examined the impact of the timing of anticoagulant resumption on the risk of delayed bleeding in high-risk therapeutic procedures. METHODS: We conducted a multicenter, prospective, observational study from January 2018 to March 2020 of 1602 patients on oral anticoagulants (1004 on VKAs and 598 on DOACs) undergoing 1874 elective endoscopic procedures. Our primary outcomes were 90-day thromboembolic events and 30-day endoscopy-related gastrointestinal bleeding. The inverse probability of treatment weighting propensity score method was used for baseline covariate adjustment. RESULTS: The 2 groups had similar risks of endoscopy-related gastrointestinal bleeding (VKAs vs DOACs, 6.2% vs 6.7%; adjusted odds ratio [OR], 1.05; 95% CI, 0.67-1.65) and thromboembolic events (VKAs vs DOACs, 1.3% vs 1.5%; adjusted OR, 0.90; 95% CI, 0.34-2.38). In high bleeding risk procedures (n = 747), delayed anticoagulant resumption (> 48 hours or 24-48 hours vs < 24 hours) did not reduce the risk of postprocedural bleeding (10.3%, 9%, and 5.8%, respectively; adjusted P = .43). Hot and cold snare polypectomy were the most frequent high-risk interventions (41.8% and 39.8%, respectively). CONCLUSION: In a prospective study of patients on DOACs or VKAs undergoing elective endoscopy, endoscopy-related bleeding and thromboembolic events showed similar risk. Our study suggests that early anticoagulant resumption is safe in most patients, but more data are needed for advanced high-risk therapeutic procedures.

pH-Responsive Metal-Organic Framework Thin Film for Drug Delivery.

In this work, surface-supportive MIL-88B(Fe) was explored as a pH-stimuli thin film to release ibuprofen as a model drug. We used surface plasmon resonance microscopy to study the pH-responsive behaviors of MIL-88B(Fe) film in real time. A dissociation constant of (6.10 ± 0.86) × 10-3 s-1 was measured for the MIL-88B(Fe) film in an acidic condition (pH 6.3), which is about 10 times higher than the dissociation of the same film in a neutral pH condition. MIL-88B(Fe) films are also capable of loading around 6.0 µg/cm2 of ibuprofen, which was measured using a quartz crystal microbalance (QCM). Drug release profiles were compared in both acidic and neutral pH conditions (pH 6.3 and 7.4) using a QCM cell to model the drug release in healthy body systems and those containing inflammatory tissues or cancerous tumors. It was found that the amount of drug released in acidic environments had been significantly higher compared to that in a neutral system within 55 h of testing time. The pH-sensitive chemical bond breaking between Fe3+ and the carboxylate ligands is the leading cause of drug release in acidic conditions. This work exhibits the potential of using MOF thin films as pH-triggered drug delivery systems.

Iron-containing metal-organic framework thin film as a drug delivery system.

Selective bulk metal-organic frameworks (MOFs) have exhibited great potential in biomedical applications. However, topical treatments and drug elution coatings will require uniform films as drug delivery systems. This work studies the use of surface supportive MOF thin films for drug loading and releasing. More specifically, we focus on an iron-containing MOF, MIL-88B(Fe), on a COOH-terminated self-assembled monolayer (SAM) modified Au surface for encapsulating ibuprofen as a model drug. A combined experimental and computational approach was employed to study the fabrication of MIL-88B(Fe) film on functionalized Au surfaces. We used several surface characterization techniques, including infrared spectroscopy and scanning electron microscopy, to confirm the chemical composition and morphological changes of the surface after each modification step. The resulting MIL-88B(Fe) thin film was found capable of loading 8.7 wt% of ibuprofen using quartz crystal microbalance analysis. Moreover, we applied cluster simulations to study the binding mechanisms of MIL-88B(Fe) and its interactions with ibuprofen based on the density functional theory (DFT). The unsaturated Fe site was confirmed kinetically more favorable to bind to the COOH-end group on the SAM. Hydrogen bonding and π-CH interactions between ibuprofen and MIL-88B(Fe) promote ibuprofen being retained inside of the cages of MIL-88B(Fe).

Discovery and 3D imaging of a novel ΔNp63-expressing basal cell type in human pancreatic ducts with implications in disease.

OBJECTIVE: The aggressive basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) harbours a ΔNp63 (p40) gene expression signature reminiscent of a basal cell type. Distinct from other epithelia with basal tumours, ΔNp63+ basal cells reportedly do not exist in the normal pancreas. DESIGN: We evaluated ΔNp63 expression in human pancreas, chronic pancreatitis (CP) and PDAC. We further studied in depth the non-cancerous tissue and developed a three-dimensional (3D) imaging protocol (FLIP-IT, Fluorescence Light sheet microscopic Imaging of Paraffin-embedded or Intact Tissue) to study formalin-fixed paraffin-embedded samples at single cell resolution. Pertinent mouse models and HPDE cells were analysed. RESULTS: In normal human pancreas, rare ΔNp63+ cells exist in ducts while their prevalence increases in CP and in a subset of PDAC. In non-cancer tissue, ΔNp63+ cells are atypical KRT19+ duct cells that overall lack SOX9 expression while they do express canonical basal markers and pertain to a niche of cells expressing gastrointestinal stem cell markers. 3D views show that the basal cells anchor on the basal membrane of normal medium to large ducts while in CP they exist in multilayer dome-like structures. In mice, ΔNp63 is not found in adult pancreas nor in selected models of CP or PDAC, but it is induced in organoids from larger Sox9low ducts. In HPDE, ΔNp63 supports a basal cell phenotype at the expense of a classical duct cell differentiation programme. CONCLUSION: In larger human pancreatic ducts, basal cells exist. ΔNp63 suppresses duct cell identity. These cells may play an important role in pancreatic disease, including PDAC ontogeny, but are not present in mouse models.

Improved short-term outcomes of kidney transplants in controlled donation after the circulatory determination of death with the use of normothermic regional perfusion.

Normothermic regional perfusion (NRP) allows the in situ perfusion of organs with oxygenated blood in donation after the circulatory determination of death (DCDD). We aimed at evaluating the impact of NRP on the short-term outcomes of kidney transplants in controlled DCDD (cDCDD). This is a multicenter, nationwide, retrospective study comparing cDCDD kidneys obtained with NRP versus the standard rapid recovery (RR) technique. During 2012-2018, 2302 cDCDD adult kidney transplants were performed in Spain using NRP (n = 865) or RR (n = 1437). The study groups differed in donor and recipient age, warm, and cold ischemic time and use of ex situ machine perfusion. Transplants in the NRP group were more frequently performed in high-volume centers (≥90 transplants/year). Through matching by propensity score, two cohorts with a total of 770 patients were obtained. After the matching, no statistically significant differences were observed between the groups in terms of primary nonfunction (p = .261) and mortality at 1 year (p =  .111). However, the RR of kidneys was associated with a significantly increased odds of delayed graft function (OR 1.97 [95% CI 1.43-2.72]; p < .001) and 1-year graft loss (OR 1.77 [95% CI 1.01-3.17]; p = .034). In conclusion, compared with RR, NRP appears to improve the short-term outcomes of cDCDD kidney transplants.

Outcomes From Brain Death Donors With Previous Cardiac Arrest Accepted for Pancreas Transplantation: A Single-center Retrospective Analysis.

OBJECTIVE: The aim of the study was to evaluate the effect of cardiac arrest time (CAT) in donors after brain death (DBD) donors on pancreas transplant outcome. SUMMARY OF BACKGROUND DATA: Results from donors after circulatory death report good outcomes despite warm ischemia times up to 57 minutes. Previous cardiac arrest in DBD has been addressed as a potential risk factor, but duration of the CAT has never been evaluated. METHODS: We conducted a retrospective analysis including 342 pancreas transplants performed at our center from 2000 to 2016, and evaluated the effect of previous cardiac arrest in DBD (caDBD) on pancreas transplant outcomes. RESULTS: A total of 49 (14.3%) caDBD were accepted for transplantation [median CAT of 5.0 min (IQR 2.5-15.0)]. Anoxic encephalopathy was most frequent and P-PASS higher (16.9 vs 15.6) in caDBD group when compared with other DBD. No differences were found in all other characteristics evaluated.Graft survival was similar between both groups, as was the incidence of early graft failure (EGF). CAT increased the risk for EGF [OR 1.09 (95% CI, 1.01-1.17)], and the duration of CPR discriminated for EGF [AUC of 0.86 (95% CI, 0.74-0.98)], with a sensitivity and specificity of 100% and 75% at a cutoff of 15 minutes. When evaluated separately, caDBD >15 min increased over 5 times the risk for EGF [HR 5.80 (95% CI, 1.82-18.56); P = 0.003], and these presented fewer days on the ICU (1.0 vs 3.0 d). CONCLUSION: CaDBD donors are suitable for routine pancreas transplantation without increasing EGF risk, and in those with longer CAT it may be prudent to postpone donation a few days to allow a thorough evaluation of organ damage following cardiac arrest.

Is antivitamin K reversal required in patients with cirrhosis undergoing liver transplantation?

BACKGROUND: Antivitamin K agent (AVK) reversal in patients with cirrhosis awaiting liver transplantation (LT) is not defined in guidelines. We investigated the effect of reversion with prothrombin complex concentrate (PCC) on intraoperative transfusion, bleeding, and safety in LT patients on AVK. STUDY DESIGN AND METHODS: In 511 patients undergoing LT, we identified 25 patients treated with AVK (AVK group) and 13 patients with incidental portal vein thrombosis (PVT) without AVK (incidental PVT group). Fifty patients who underwent LT without PVT or AVK matched by age, model for end stage of liver disease (MELD), body mass index (BMI), and cirrhosis etiology were selected as the control group. RESULTS: There were no significant differences between the three groups in intraoperative blood loss, transfusion, and postoperative bleeding. In the AVK group, there were no differences between patients who received PCC and those who did not in intraoperative blood loss, red blood cells, fibrinogen, and platelet transfusion, or postoperative bleeding. PCC use had no effect on RBC transfusion in patients who had international normalized ratio or clotting time above versus below median values of the two parameters at baseline (2.3 and 103 s, respectively). No thrombotic events were detected in patients who received PCC. DISCUSSION: These data suggest that systematic administration of PCC to revert AVK prior to LT should be reconsidered.

Fast pyrolysis as an alternative to the valorization of olive mill wastes.

BACKGROUND: The valorization of organic wastes through fast pyrolysis appears to be a highly promising option for decreasing pollutants and reducing consumption of natural resources. For this purpose, three different olive pomace samples were studied to determine how olive crop location and the extraction process could influence bio-oil product distribution. Olive pomace was selected as the feedstock due to the importance of the olive oil industry in Spain. RESULTS: In this study, the conditions of fast pyrolysis were optimized using lignin as a reference, with the optimum conditions being 500 °C, 20 °C ms-1 as the heating rate and 15 s as the vapour residence time. The olive pomace results determined that not only their chemical composition, but also their fat content had a remarkable effect on product distribution obtained after fast pyrolysis. However, whereas high lignin content enhanced phenol production, cellulose decomposed to carboxylic acids. In addition, due to current global warming, the carbon dioxide (CO2 ) burden of the three samples was calculated using mass spectroscopy. The OPGC sample gave off the lowest amount of greenhouse gases, followed by OPMNE and OPMN. CONCLUSIONS: The higher fat content in the sample enhanced carboxylic acid production. The difference in phenol production between OPMN and OPMNE could be attributed to the presence of potassium. From an environmental point of view, the use of olive pomace wastes could reduce CO2 emissions with further research and by developing experimental processes. © 2020 Society of Chemical Industry.

Long-term follow-up after endoscopic submucosal dissection of colorectal lesions in a Spanish cohort.

INTRODUCTION: ESD in the colon is an increasingly important technique in Western countries. There are few studies that include long term follow-up. AIM: to analyze the long term recurrence free survival rate after ESD and to compare recurrence rates according to different variables. METHODS: this was a prospective observational study of patients with a planned ESD from September 2008 to December 2015. When it was not possible to achieve an ESD, hybrid ESD was performed, either en bloc or piecemeal. Kaplan-Meier survival curves were used to assess the five year local recurrence free survival rate and the recurrence rate. The results were compared according to different factors. RESULTS: of the 89 patients scheduled for ESD who were initially enrolled in the study, 69 were finally included for follow-up. ESD was performed in 31 (45%) patients, KAR in eleven (16%) and pKAR in 27 (39%). The median follow-up was 27 months (range 6-60). The five year disease free survival rate was 81%. The average number of endoscopies needed to eliminate recurrence was two (range 2-7) and no patient required surgery for this reason. The recurrence rate was significantly higher in piecemeal resections vs en bloc resections (27% vs 15%, p = 0.036) and R1 resections vs R0 resections (26% vs 0%, p = 0.034). The presence of affected or unknown lateral margins in en bloc resections without other poor prognosis factors had higher recurrence rates but the difference was not statistically significant (28% vs 0%, p = 0.09). CONCLUSIONS: in our study, the five year disease free survival rate was 81% and no patient required surgery during follow-up. Piecemeal and R1 resections had significantly higher recurrence rates, as well as LM involvement, although this was not statistically significant.

Endoscopic submucosal dissection for gastric epithelial lesions: long-term results in a Spanish cohort.

INTRODUCTION: endoscopic submucosal dissection for gastric lesions (ESD-G) is a technique that allows en-bloc resection of early gastric tumors, with a cure rate similar to that of surgery but lower morbidity and mortality rates. OBJECTIVE: to assess total survival, disease-free survival and relapse rate during the course of disease in a Spanish cohort of patients undergoing ESD-G. MATERIAL AND METHODS: this was a prospective observational study of patients undergoing ESD-G from 2008 to 2015, with a follow-up ranging from six to 60 months. Recurrence at five years was analyzed using Kaplan-Meier curves and the results were compared according to several factors using the log-rank test. These included en-bloc versus piecemeal resection and R0 curative resection versus resection with affected lateral margins (LM+). RESULTS: a total of 35 patients undergoing ESD-G were assessed, with a median follow-up of 33.62 months. Four relapses were identified (11.4%) during this period, of which three were managed with repeat ESD-G. A histological specimen with LM+ was associated with a higher local relapse rate during follow-up (p = 0.06). Piecemeal resections had a higher relapse risk, although no statistically significant differences were identified (p = 0.49). No deaths from gastric cancer occurred and no gastrectomies due to persistent disease were performed during this period. The overall survival rate in our series was 94.3%. CONCLUSIONS: ESD-G in our setting provides high long-term cure rates, while avoiding surgery. These results are similar to those reported by the European series and remain far removed from the cure and relapse rates obtained in Asian cohorts. Local relapse cases may be monitored with endoscopy.

Kidney transplantation from donors after uncontrolled circulatory death: the Spanish experience.

Donation after uncontrolled circulatory death (uDCD) refers to donation from persons who have died following cardiac arrest and unsuccessful attempt at resuscitation. We report the Spanish experience of uDCD kidney transplantation, and identify factors related to short-term post-transplant outcomes. The Spanish CORE system compiles data on all donation and transplant procedures in the country. Between 2012-2015, 517 kidney transplants from 288 uDCD donors were performed. The incidence of primary non-function was 10%, and the incidence of delayed graft function was 76%. One-year death-censored graft survival was 87%. In a Cox-Model, donor age ≥ 60 years (odds ratio [OR] 2.7; 95% confidence interval [CI] 1.2-6.1), in situ cooling of kidneys versus normothermic regional perfusion (OR 5.6; 95% CI 2.7-11.5) or hypothermic regional perfusion based on the use of extracorporeal membrane oxygenation devices (OR 4.3; 95% CI 2.1-8.6), and a recipient history of prior kidney transplant (OR 3.5; 95% CI 1.5-8.3) all significantly increased the risk of graft loss during the first year after transplantation. Kidney transplantation from uDCD donors provides acceptable 1-year outcomes, although there is room for improvement. Hypothermic and normothermic regional perfusion strategies are preferable to in situ cooling of kidneys from uDCD donors.

The development of a predictive model of graft function in uncontrolled donors after circulatory death: validity of a pulsatile renal preservation machine cut-off value for kidney acceptance.

BACKGROUND: The criteria for kidney suitability in uncontrolled donors after circulatory death (uDCD) procured after regional normothermic perfusion are based on macroscopic appearance and renal haemodynamic values with final renal resistance (FRR). However, these criteria have not been analysed to predict the future graft function. This study presents a model to predict the outcome in uDCD kidneys and define the predictive FRR value. METHODS: All uDCD kidney transplants performed in our hospital from 2004 to 2016 were included. Donors and recipients and pre-transplantation data are described. The endpoint was glomerular filtration rate (GFR) ≥30 mL/min at 6 months after transplantation. RESULTS: A total of 194 recipients were included. FRR in donors ≥60 years old was (mean ± SD) 0.27 ± 0.11 versus 0.22 ± 0.09 mmHg/mL/min in donors <60 years (P = 0.042). Kidney survival was 88.2% versus 84% at 12 months and 60.7% versus 30.8% at 120 months (P = 0.067). For the group of recipients from donors ≥60 years, the FRR was 0.37 ± 0.08 mmHg/mL/min in the GFR <30 mL/min group versus 0.18 ± 0.06 mmHg/mL/min in the GFR ≥30 mL/min group (P < 0.001). The value FRR ≥0.3 mmHg/mL/min predicts 59-79% of GFR <30 mL/min [odds ratio = 2.16, 95% confidence interval (CI) 1.80-6.40; P < 0.001]. The predictive accuracy of FRR for GFR by ROC curve was 0.968 (95% CI). The best cut-off for FRR was 0.3 mmHg/mL/min to predict GFR at 6 months with a sensitivity of 67%, specificity of 100%, positive predictive value of 83% and negative predictive value of 92%. CONCLUSIONS: Our results suggest that in uDCD donors the combination of donor age ≥60 years together with FRR ≥0.3 mmHg/mL/min could predict poor outcome at 6 months after transplantation in low immunological risk recipients.

Evolution Under Normothermic Machine Perfusion of Type 2 Donation After Cardiac Death Livers Discarded as Nontransplantable.

BACKGROUND: Type 2 donation after cardiac death (DCD) represents an underused source of grafts for liver transplantation. In our center, normothermic regional perfusion and strict selection criteria have led to acceptable postoperative results after transplanting type 2 DCD livers. However, many of these grafts are still discarded before transplantation. We believe that the suitability of these organs may be improved by adding normothermic machine perfusion (NMP) to our current procedure. MATERIALS AND METHODS: A total of 5 type 2 DCD livers discarded for transplantation were submitted to normothermic regional perfusion and 12 h of NMP. The macroscopic aspect of the liver, vascular and bile flows, and pH were continuously monitored. Serial perfusate analyses and liver biopsies were performed. After NMP, the microscopic appearance of the liver parenchyma and the bile ducts was analyzed. RESULTS: All the grafts showed hemodynamic stability during the NMP. The alanine aminotransferase peak during NMP correlated with the warm ischemia time (Pearson correlation of 0.933, p 0.021). After an initial period of acidosis, the grafts were generally able to spontaneously correct pH and lactate levels without the need for additional bicarbonate. Livers with favorable bile duct histology generally started bile production earlier and registered higher bile flows. CONCLUSIONS: NMP represents a feasible procedure for use with type 2 DCD livers. The pH and lactate correction and the bile flows appear to be significant factors associated with graft viability. However, these favorable results should be confirmed in a clinical transplant setting.

Single nanowire measurements of room temperature ferromagnetism in FeSi nanowires and the effects of Mn-doping.

Semiconductors with magnetic response at room temperature are sought for spintronics in solid-state devices. Among possible materials for this applications, the magnetic response of FeSi and doped FeSi have produced contradictory results at the nanoscale and more precise measurements and deeper studies are needed to clarify its potential capabilities. For that reason, in this work, single nanowire measurements of ferromagnetic semiconducting FeSi and Mn-doped FeSi nanostructures have been performed using magnetic force microscopy and electron holography. Results obtained confirm the presence of magnetic domains at room temperature with a magnetic moment per Fe atom of [Formula: see text] Spin polarized density functional calculations confirm a net magnetic moment between [Formula: see text] in Fe surface atoms with an estimated Curie temperature of 417 K by means of the molecular field approximation. The nanowires present a crystalline B20 cubic structure as confirmed by x-ray diffraction and high-resolution electron microscopy. Their electrical transport measurements confirm p-type nature and thermal activation. A remanent magnetization of 1.5 × 10-5 emu and 0.5 × 10-5 emu was measured at room temperature for FeSi and Mn-doped FeSi respectively, with spin freezing behavior around 30 K for the Mn-doped nanowires.

A Novel Noninvasive Approach Based on SPECT and EEG for the Location of the Epileptogenic Zone in Pharmacoresistant Non-Lesional Epilepsy.

Background and objectives: The aim of this study is to propose a methodology that combines non-invasive functional modalities electroencephalography (EEG) and single photon emission computed tomography (SPECT) to estimate the location of the epileptogenic zone (EZ) for the presurgical evaluation of patients with drug-resistant non-lesional epilepsy. Materials and Methods: This methodology consists of: (i) Estimation of ictal EEG source imaging (ESI); (ii) application of the subtraction of ictal and interictal SPECT co-registered with MRI (SISCOM) methodology; and (iii) estimation of ESI but using the output of the SISCOM as a priori information for the estimation of the sources. The methodology was implemented in a case series as an example of the application of this novel approach for the presurgical evaluation. A gold standard and a coincidence analysis based on measures of sensitivity and specificity were used as a preliminary assessment of the proposed methodology to localize EZ. Results: In patients with good postoperative evolution, the estimated EZ presented a spatial coincidence with the resection site represented by high values of sensitivity and specificity. For the patient with poor postoperative evolution, the methodology showed a partial incoherence between the estimated EZ and the resection site. In cases of multifocal epilepsy, the method proposed spatially extensive epileptogenic zones. Conclusions: The results of the case series provide preliminary evidence of the methodology's potential to epileptogenic zone localization in non-lesion drug-resistant epilepsy. The novelty of the article consists in estimating the sources of ictal EEG using SISCOM result as a prior for the inverse solution. Future studies are necessary in order to validate the described methodology. The results constitute a starting point for further studies in order to support the clinical reliability of the proposed methodology and advocate for their implementation in the presurgical evaluation of patients with intractable non-lesional epilepsy.

Heparin but not tissue plasminogen activator improves outcomes in donation after circulatory death liver transplantation in a porcine model.

Ischemic-type biliary lesions (ITBLs) arise most frequently after donation after circulatory death (DCD) liver transplantation and result in high morbidity and graft loss. Many DCD grafts are discarded out of fear for this complication. In theory, microvascular thrombi deposited during donor warm ischemia might be implicated in ITBL pathogenesis. Herein, we aim to evaluate the effects of the administration of either heparin or the fibrinolytic drug tissue plasminogen activator (TPA) as means to improve DCD liver graft quality and potentially avoid ITBL. Donor pigs were subjected to 1 hour of cardiac arrest (CA) and divided among 3 groups: no pre-arrest heparinization nor TPA during postmortem regional perfusion; no pre-arrest heparinization but TPA given during regional perfusion; and pre-arrest heparinization but no TPA during regional perfusion. In liver tissue sampled 1 hour after CA, fibrin deposition was not detected, even when heparin was not given prior to arrest. Although it was not useful to prevent microvascular clot formation, pre-arrest heparin did offer cytoprotective effects during CA and beyond, reflected in improved flows during regional perfusion and better biochemical, functional, and histological parameters during posttransplantation follow-up. In conclusion, this study demonstrates the lack of impact of TPA use in porcine DCD liver transplantation and adds to the controversy over whether the use of TPA in human DCD liver transplantation really offers any protective effect. On the other hand, when it is administered prior to CA, heparin does offer anti-inflammatory and other cytoprotective effects that help improve DCD liver graft quality. Liver Transplantation 24 665-676 2018 AASLD.