Assessing teratogenic risks of gadolinium in freshwater environments: Implications for environmental health.

Gadolinium (Gd) is among the rare earth elements extensively utilized in both industrial and medical applications. The latter application appears to contribute to the rise in Gd levels in aquatic ecosystems, as it is excreted via urine from patients undergoing MRI scans and often not captured by wastewater treatment systems. The potential environmental and biological hazards posed by gadolinium exposure are still under investigation. This study aimed to assess the teratogenic risk posed by a gadolinium chelate on the freshwater cnidarian Hydra vulgaris. The experimental design evaluated the impact of pure Gadodiamide (25 µg/l, 50 µg/l, 100 µg/l, 500 µg/l) and its commercial counterpart compound (Omniscan®; 100 µg/l, 500 µg/l, 782.7 mg/l) at varying concentrations using the Teratogenic Risk Index (TRI). Here we showed a moderate risk (Class III of TRI) following exposure to both tested formulations at concentrations ≥ 100 µg/l. Given the potential for similar concentrations in aquatic environments, particularly near wastewater discharge points, a teratogenic risk assessment using the Hydra regeneration assay was conducted on environmental samples collected from three rivers (Tiber, Almone, and Sacco) in Central Italy. Additionally, chemical analysis of field samples was performed using ICP-MS. Analysis of freshwater samples revealed low Gd concentrations (≤ 0.1 µg/l), despite localized increases near domestic and/or industrial wastewater discharge sites. Although teratogenic risk in environmental samples ranged from high (Class IV of TRI) to negligible (Class I of TRI), the low Gd concentrations, particularly when compared to higher levels of other contaminants like arsenic and heavy metals, preclude establishing a direct cause-effect relationship between Gd and observed teratogenic risks in environmental samples. Nevertheless, the teratogenic risks observed in laboratory tests warrant further investigation.

Influence of stimuli emotional features and typicality on memory performance: insights from a virtual reality context.

The present study tested the influence of stimuli emotional valence, emotional arousal, and typicality on memory recollection in three groups of participants exposed to the same environment through different modalities: in vivo exposure (i.e., real-life), 3D virtual reality (i.e., VR), and 2D pictures. Context-related free-recall, recognition accuracy, and recognition confidence were analyzed. The results showed that memory performance was best in the real-life modality, and participants in the VR and 2D pictures modalities performed comparably. Interesting effects of stimuli emotional valence and typicality emerged: in the VR and 2D pictures modalities, positive items were better recalled than negative items; typicality was relevant only in the real-life modality, with less common objects within the explored setting (i.e., an office) recalled more often. Furthermore, recognition accuracy and confidence were significantly higher in the real-life modality than in the VR and 2D pictures modalities. Further research is needed to support the creation of VR environments that are sufficiently comparable to real-life contexts in order to obtain higher ecological validity in studies of cognitive performance. In particular, the impact of stimuli typicality and emotional valence in VR contexts should be investigated to gain insight into how these features might improve memory recall in virtual scenarios.

External validation of scores predicting postoperative fistula after pancreatogastrostomy for pancreatoduodenectomy reconstruction. A single center experience.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is the most frequent complication of pancreatic surgery and can be fatal. Selection and stratification of patients according to the risk of POPF are important for the perioperative management. Predictive metrics have been developed and validated in pancreatojejunostomy. Aim of this study is to assess whether the most used prognostic scores can be predictive of fistula following Wirsung-pancreaticogastrostomy (WPG) for pancreatoduodenectomy (PD)reconstruction. METHOD: This single-center prospective observational study included 212 PDs between January 2008 and October 2022 with a standardized WPG. All component variables of the six scores were separately validated in our cohort. The overall predictive ability of the six fistula scores was measured and compared with the receiver operating characteristics curves (ROC) method and expressed by the area under the ROC-curve (AUC). Univariate and multivariate logistic regression analyses were performed considering all risk factors in the scores in order to identify variables independently correlated with POPF in the WPG. RESULTS: CR-POPF occurred in 36 of 212 (17 %) patients. All scores showed poor prognostic stratification for the development of CR-POPF. The occurrence of CR-POPF was associated with nine factors: male gender (p = 0.003); BMI (kg/m2) (p = 0.005); ASA (%) (p = 0.003); Soft pancreatic texture (%) (p = 0.003), Pathology (p = 0.008); MPD (p = 0.011); EBL (mL) (p = 0.021); Preop. Bilirubin (mg/dl) (p = 0.038); Preop. Glucose (mg/dl) (p = 0.0369). Male gender (OR: 5.54, CI 1.41-21.3) and soft consistency of the remnant pancreas (OR: 3.83, CI 1.14-12.8) were the only independent prognostic factors on multivariate analysis. CONCLUSIONS: Our study including exclusively pancreatogastrostomies failed to validate the most used predictive scores for POPF. We found that only male gender and soft pancreatic texture are associated with POPF. Specific predictive scores following pancreatogasgtrostomy are needed.

Minimally Invasive Surgery for Perihilar Cholangiocarcinoma: A Systematic Review of the Short- and Long-Term Results.

Surgery and postoperative systemic chemotherapy represent the standard treatment for patients with perihilar cholangiocarcinoma (PHC). Minimally Invasive Surgery (MIS) for hepatobiliary procedures has spread worldwide in the last two decades. Since resections for PHC are technically demanding, the role of MIS in this field is yet to be established. This study aimed to systematically review the existing literature on MIS for PHC, to evaluate its safety and its surgical and oncological outcomes. A systematic literature review on PubMed and SCOPUS was performed according to the PRISMA guidelines. Overall, a total of 18 studies reporting 372 MIS procedures for PHC were included in our analysis. A progressive increase in the available literature was observed over the years. A total of 310 laparoscopic and 62 robotic resections were performed. A pooled analysis showed an operative time ranging from 205.3 ± 23.9 and 840 (770-890) minutes, and intraoperative bleeding between 101.1 ± 13.6 and 1360 ± 809 mL. Minor and major morbidity rates were 43.9% and 12.7%, respectively, with a 5.6% mortality rate. R0 resections were achieved in 80.6% of patients and the number of retrieved lymph nodes ranged between 4 (3-12) and 12 (8-16). This systematic review shows that MIS for PHC is feasible, with safe postoperative and oncological outcomes. Recent data has shown encouraging results and more reports are being published. Future studies should address differences between robotic and laparoscopic approaches. Given the management and technical challenges, MIS for PHC should be performed by experienced surgeons, in high-volume centers, on selected patients.

Iron Saturation Drives Lactoferrin Effects on Oxidative Stress and Neurotoxicity Induced by HIV-1 Tat.

The Trans-Activator of Transcription (Tat) of Human Immunodeficiency Virus (HIV-1) is involved in virus replication and infection and can promote oxidative stress in human astroglial cells. In response, host cells activate transcription of antioxidant genes, including a subunit of System Xc- cystine/glutamate antiporter which, in turn, can trigger glutamate-mediated excitotoxicity. Here, we present data on the efficacy of bovine Lactoferrin (bLf), both in its native (Nat-bLf) and iron-saturated (Holo-bLf) forms, in counteracting oxidative stress in U373 human astroglial cells constitutively expressing the viral protein (U373-Tat). Our results show that, dependent on iron saturation, both Nat-bLf and Holo-bLf can boost host antioxidant response by up-regulating System Xc- and the cell iron exporter Ferroportin via the Nuclear factor erythroid 2-related factor (Nrf2) pathway, thus reducing Reactive Oxygen Species (ROS)-mediated lipid peroxidation and DNA damage in astrocytes. In U373-Tat cells, both forms of bLf restore the physiological internalization of Transferrin (Tf) Receptor 1, the molecular gate for Tf-bound iron uptake. The involvement of astrocytic antioxidant response in Tat-mediated neurotoxicity was evaluated in co-cultures of U373-Tat with human neuronal SH-SY5Y cells. The results show that the Holo-bLf exacerbates Tat-induced excitotoxicity on SH-SY5Y, which is directly dependent on System-Xc- upregulation, thus highlighting the mechanistic role of iron in the biological activities of the glycoprotein.

Challenging Scenarios and Debated Indications for Laparoscopic Liver Resections for Hepatocellular Carcinoma.

Laparoscopic liver resections (LLRs) have been increasingly adopted for the treatment of hepatocellular carcinoma (HCC), with safe short- and long-term outcomes reported worldwide. Despite this, lesions in the posterosuperior segments, large and recurrent tumors, portal hypertension, and advanced cirrhosis currently represent challenging scenarios in which the safety and efficacy of the laparoscopic approach are still controversial. In this systematic review, we pooled the available evidence on the short-term outcomes of LLRs for HCC in challenging clinical scenarios. All randomized and non-randomized studies reporting LLRs for HCC in the above-mentioned settings were included. The literature search was run in the Scopus, WoS, and Pubmed databases. Case reports, reviews, meta-analyses, studies including fewer than 10 patients, non-English language studies, and studies analyzing histology other than HCC were excluded. From 566 articles, 36 studies dated between 2006 and 2022 fulfilled the selection criteria and were included in the analysis. A total of 1859 patients were included, of whom 156 had advanced cirrhosis, 194 had portal hypertension, 436 had large HCCs, 477 had lesions located in the posterosuperior segments, and 596 had recurrent HCCs. Overall, the conversion rate ranged between 4.6% and 15.5%. Mortality and morbidity ranged between 0.0% and 5.1%, and 18.6% and 34.6%, respectively. Full results according to subgroups are described in the study. Advanced cirrhosis and portal hypertension, large and recurrent tumors, and lesions located in the posterosuperior segments are challenging clinical scenarios that should be carefully approached by laparoscopy. Safe short-term outcomes can be achieved provided experienced surgeons and high-volume centers.

The Role of Pre-Pandemic Mental Health Status and Personality Traits on Psychological Distress during the COVID-19 Lockdown among Italian Young Adults.

The COVID-19 pandemic imposed changes on day-to-day activities and had a detrimental psychological effect on the population, especially among vulnerable individuals, such as adolescents and young adults. The current study aimed to explore variables associated with anxiety, depressive and somatic symptoms in a sample of 608 Italian young adults aged 18 to 25. Data were collected using an online questionnaire administered two months into the COVID-19 lockdown, which explored several areas including sociodemographic information, pre-pandemic and current psychological distress, pre-pandemic and current levels of loneliness, and the traits of intolerance of uncertainty and boredom susceptibility. Results highlighted that having pre-existing mental health issues, being female, and the personality traits of intolerance to uncertainty and boredom susceptibility all played a role in the psychological distress experienced during the pandemic. COVID-19 contributed to negative impacts on young adults' mental health, highlighting the necessity to develop protective psychological intervention tailored for this vulnerable population.

High Expressed Emotion (HEE), Assessed Using the Five-Minute Speech Sample (FMSS), as a Predictor of Psychiatric Relapse in Patients with Schizophrenia and Major Depressive Disorder: A Meta-Analysis and Meta-Regression.

Expressed Emotion (EE) describes the tone of a caregiver's response to a patient with a mental disorder, and it is used to predict relapse. The Five-Minute Speech Sample (FMSS) is a 5-min interview with a caregiver that evaluates only two EE dimensions. The present study aimed at evaluating HEE (High Expressed Emotion) as a predictor of relapse in patients with schizophrenia and major depressive disorder. Six studies were selected for the meta-analysis. In total, the studies included 297 subjects. The analyses included a random effects model; a meta-analysis excluding the study with the smallest sample; a cumulative meta-analysis; a meta-regression with random effects, using patient age and duration of illness as moderators; a leave-one-out meta-analysis; and a funnel plot to estimate publication bias. The FMSS emerged as a valid and reliable tool for measuring EE as a predictor of relapse in patients with schizophrenia and major depressive disorder. Patient age and duration of illness had no significant effect on the results. Future meta-analyses should include more studies to reduce publication bias. EE may be a good predictor of relapse when examined through a fast measurement technique such as the FMSS, which may also be useful to analyze the psychopathological structure of caregivers.

Splenic artery steal syndrome after liver transplantation - prophylaxis or treatment?: A case report and literature review.

Splenic artery steal syndrome (SASS) is a cause of graft hypoperfusion leading to the development of biliary tract complications, graft failure, and in some cases to retransplantation. Its management is still controversial since there is no universal consensus about its prophylaxis and consequently treatment. We present a case of SASS that occurred 48 hours after orthotopic liver transplantation (OLTx) in a 56-year-old male patient with alcoholic cirrhosis and severe portal hypertension, and who was successfully treated by splenic artery embolization. A literature search was performed using the PubMed database, and a total of 22 studies including 4,789 patients who underwent OLTx were relevant to this review. A prophylactic treatment was performed in 260 cases (6.2%) through splenic artery ligation in 98 patients (37.7%) and splenic artery banding in 102 (39.2%). In the patients who did not receive prophylaxis, SASS occurred after OLTx in 266 (5.5%) and was mainly treated by splenic artery embolization (78.9%). Splenic artery ligation and splenectomies were performed, respectively, in 6 and 20 patients (2.3% and 7.5%). The higher rate of complications registered was represented by biliary tract complications (9.7% in patients who received prophylaxis and 11.6% in patients who developed SASS), portal vein thrombosis (respectively, 7.3% and 6.9%), splenectomy (4.8% and 20.9%), and death from sepsis (4.8% and 30.2%). Whenever possible, prevention is the best way to approach SASS, considering all the potential damage arising from an arterial graft hypoperfusion. Where clinical conditions do not permit prophylaxis, an accurate risk assessment and postoperative monitoring are mandatory.

Prognostic Factors for 10-Year Survival in Patients With Hepatocellular Cancer Receiving Liver Transplantation.

Background: Long-term survival after liver transplantation (LT) for hepatocellular cancer (HCC) continues to increase along with the modification of inclusion criteria. This study aimed at identifying risk factors for 5- and 10-year overall and HCC-specific death after LT. Methods: A total of 1,854 HCC transplant recipients from 10 European centers during the period 1987-2015 were analyzed. The population was divided in three eras, defined by landmark changes in HCC transplantability indications. Multivariable logistic regression analyses were used to evaluate the significance of independent risk factors for survival. Results: Five- and 10-year overall survival (OS) rates were 68.1% and 54.4%, respectively. Two-hundred forty-two patients (13.1%) had HCC recurrence. Five- and 10-year recurrence rates were 16.2% and 20.3%. HCC-related deaths peaked at 2 years after LT (51.1% of all HCC-related deaths) and decreased to a high 30.8% in the interval of 6 to 10 years after LT. The risk factors for 10-year OS were macrovascular invasion (OR = 2.71; P = 0.001), poor grading (OR = 1.56; P = 0.001), HCV status (OR = 1.39; P = 0.001), diameter of the target lesion (OR = 1.09; P = 0.001), AFP slope (OR = 1.63; P = 0.006), and patient age (OR = 0.99; P = 0.01). The risk factor for 10-year HCC-related death were AFP slope (OR = 4.95; P < 0.0001), microvascular (OR = 2.13; P < 0.0001) and macrovascular invasion (OR = 2.32; P = 0.01), poor tumor grading (OR = 1.95; P = 0.001), total number of neo-adjuvant therapies (OR = 1.11; P = 0.001), diameter of the target lesion (OR = 1.11; P = 0.002), and patient age (OR = 0.97; P = 0.001). When analyzing survival rates in function of LT era, a progressive improvement of the results was observed, with patients transplanted during the period 2007-2015 showing 5- and 10-year death rates of 26.8% and 38.9% (vs. 1987-1996, P < 0.0001; vs. 1997-2006, P = 0.005). Conclusions: LT generates long-term overall and disease-free survival rates superior to all other oncologic treatments of HCC. The role of LT in the modern treatment of HCC becomes even more valued when the follow-up period reaches at least 10 years. The results of LT continue to improve even when prudently widening the inclusion criteria for transplantation. Despite the incidence of HCC recurrence is highest during the first 5 years post-transplant, one-third of them occur later, indicating the importance of a life-long follow-up of these patients.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for advanced hepatocellular carcinoma with macrovascular invasion.

Patients with advanced hepatocellular carcinoma (HCC) and macrovascular invasion (MVI) have dismal prognosis and are referred to systemic treatment or palliation. To investigate the outcomes of patients with HCC and MVI undergoing the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure. Demographics and operative data were retrospectively reviewed. All types of hepatectomies and all types of ALPPS modifications were included. MVI was categorized according to the Japanese Liver Cancer Study Group classification. 28 patients were included. Viral aetiology was the most common cause of chronic liver disease (89.3%). 85.7% of patients were cirrhotic, with a median MELD score of 9 (7-10). MVI of the hepatic veins or inferior vena cava was diagnosed in 46.4% of patients while portal vein involvement was present in 64.2% of cases. Four patients (14.2%) were diagnosed with bile duct involvement. No patients died after Step 1 while complications occurred in 21.4% of cases. Following step 2, 3 patients (11.5%) died and 20 (69.2%) developed complications. Grade B and C post-hepatectomy liver failure occurred in 57.6% and 11.5% of patients, respectively. After a median follow-up of 18 months (7-35), median survival was 22 months (3-40). Eleven patients (39.3%) recurred. Median disease-free survival was 15 months (5-26). The ALPPS procedure is an extreme rescue approach in otherwise inoperable advanced HCC with MVI. The procedure is associated with high morbidity and mortality and patients' selection is pivotal. Oncological outcomes are safe and should be further investigated.

Laparoscopic Left Hepatectomy for Hepatocellular Carcinoma Recurrence Following Liver Transplantation.

BACKGROUND: Despite the successful oncological results of liver transplantation, patients with hepatocellular carcinoma (HCC) can develop tumor recurrence. When technically feasible, liver resection represents the preferred treatment for recurrent HCC, even in the setting of transplanted patients. Recent progresses in minimally invasive liver resections have pushed the surgical community to attempt more challenging cases. We report a full laparoscopic left hepatectomy for HCC recurrence on transplanted liver. METHODS: A routine follow-up computed tomography (CT) scan of a 53-year-old male who previously underwent an orthotopic liver transplantation for alcoholic-related liver disease showed a 3 cm HCC in segment 4 in close relationship with the peripheral portion of the left portal pedicle. A full laparoscopic left hepatectomy was performed using an extrahepatic intraglissonean approach. RESULTS: Operative time was 332 min and blood loss was 100 mL. The patient had an uneventful postoperative recovery and was discharged home after 3 days. CONCLUSIONS: Laparoscopic liver resection on transplanted patients is feasible. Challenging clinical scenarios should only be attempted in referral centers and after an appropriate learning curve.1-8.

How Has COVID-19 Affected Mental Health and Lifestyle Behaviors after 2 Years? The Third Step of a Longitudinal Study of Italian Citizens.

The COVID-19 pandemic and its protective measures had a tremendous effect on the general population's mental health and deeply affected their lifestyle. The present study carried out a longitudinal analysis to evaluate the long-lasting psychological effects of the pandemic and its impact on the general population's day-to-day routine. Three points in time were considered: the initial period of the lockdown (T1; n = 2766; March 2020), the final period of the lockdown (T2; n = 439; May 2020) and two years after the lockdown (T3; n = 268; July 2022). Frequency analyses were carried out to examine which behavioral changes were maintained following the COVID-19 pandemic and lockdown; furthermore, a repeated measures ANOVA test was run to measure differences in depression, stress, and anxiety levels between the three periods considered; lastly, multivariable ordinal logistic regression analyses were carried out to examine which variables were associated with psychological distress more than two years after the lockdown. The results highlighted that depression at T3 was associated with depression at T2 and negative affect, whereas stress at T3 was associated with stress at T2 and detachment. The psychological effects and lifestyle changes are also discussed.

Is minimally invasive liver surgery a reasonable option in recurrent HCC? A snapshot from the I Go MILS registry.

Laparoscopic liver resection (LLR) for Hepatocellular carcinoma (HCC) is a safe procedure. Repeat surgery is more often required, and the role of minimally invasive liver surgery (MILS) is not yet clearly defined. The present study analyzes data compiled by the Italian Group of Minimally Invasive Liver Surgery (IGoMILS) on LLR. To compare repeated LLR with the first LLR for HCC is the primary endpoint. The secondary endpoint was to evaluate the outcome of repeat LLR in the case of primary open versus primary MILS surgery. The data cohort is divided into two groups. Group 1: first liver resection and Group 2: Repeat LLR. To compare the two groups a 3:1 Propensity Score Matching is performed to analyze open versus MILS primary resection. Fifty-two centers were involved in the present study, and 1054 patients were enrolled. 80 patients underwent to a repeat LLR. The type of resection was different, with more major resections in the group 1 before matching the two groups. After propensity score matching 3:1, each group consisted of 222 and 74 patients. No difference between the two groups was observed. In the subgroup analysis, in 44 patients the first resection was performed by an open approach. The other 36 patients were resected with a MILS approach. We found no difference between these two subgroups of patients. The present study in repeat MILS for HCC using the IGoMILS Registry has observed the feasibility and safety of the MILS procedure.

Outcomes comparison of Pancreato-Gastrostomy and Isolated Jejunal Loop Pancreato-Jejunostomy following Pancreato-Duodenectomy in patients with soft pancreas and at moderate-high risk for POPF: a retrospective multicenter experience-based analysis.

Following pancreatoduodenectomy (PD), the modality of pancreato-enteric continuity restoration may impact on postoperative pancreatic fistula (POPF) risk. The aim of this study is to compare, among patients with soft pancreas and at moderate/high risk for POPF, the outcomes of PD with Pancreato-Gastrostomy (PG), versus Isolated Jejunal Loop Pancreato-Jejunostomy (IJL-PJ). 193 patients with a Callery Fistula Risk Score (C-FRS) ≥ 3 operated at 3 HPB Units, two performing PG and one IJL-PJ as their preferred anastomotic technique following PD (2009-2019) were included in this study (PG = 123, IJL-PJ = 70). Primary outcomes were POPF, clinically relevant (cr-)postoperative pancreatic hemorrhage (cr-PPH), delayed gastric emptying (cr-DGE), and postoperative major complications and mortality. POPF, cr-PPH, and cr-DGE occurred in 21.8%, 17.6%, and 11.4% of patients, and did not differ significantly between PG (26%, 19.5%, and 10.6%, respectively) and IJL-PJ (17.1%, 14.3%, and 12.9%, respectively; all p > 0.05) patients. Major (Dindo ≥ 3) complication and mortality rates were 26.4% and 3.3%, respectively, and did not differ significantly between PG (29.3% and 3.8%) and IJL-PJ (21.4% and 2.9) patients (p > 0.05). A faster surgical drain and nasogastric tube removal matched a significantly shorter hospitalization among IJL-PJ patients (median LOS: 18 days versus 25 days among PG patients, p < 0.001). In conclusion, IJL-PJ and PG, when performed by surgeons specialized with the concerned anastomotic technique in patients with soft pancreas and moderate/high risk for POPF, have similar results in terms of perioperative mortality and postoperative complications both overall and specific for PD.

The Applications of 3D Imaging and Indocyanine Green Dye Fluorescence in Laparoscopic Liver Surgery.

Laparoscopic liver resections have gained widespread popularity among hepatobiliary surgeons and is nowadays performed for both standard and more complex hepatectomies. Given the increased technical challenges, preoperative planning and intraoperative guidance is pivotal in laparoscopic surgery to safely carry out complex and oncologically safe hepatectomies. Modern tools can help both preoperatively and intraoperatively and allow surgeons to perform more precise hepatectomies. Preoperative 3D reconstructions and printing as well as augmented reality can increase the knowledge of the specific anatomy of the case and therefore plan the surgery accordingly and tailor the procedure on the patient. Furthermore, the indocyanine green retention dye is an increasingly used tool that can nowadays improve the precision during laparoscopic hepatectomies, especially when considering anatomical resection. The use of preoperative modern imaging and intraoperative indocyanine green dye are key to successfully perform complex hepatectomies such as laparoscopic parenchymal sparing liver resections. In this narrative review, we discuss the aspects of preoperative and intraoperative tools that are nowadays increasingly used in experienced hepatobiliary centers.

Amyloid-ß 25-35 Induces Neurotoxicity through the Up-Regulation of Astrocytic System Xc.

Amyloid-ß (Aß) deposition, a hallmark of Alzheimer's disease, is known to induce free radical production and oxidative stress, leading to neuronal damage. During oxidative stress, several cell types (including astrocytes) can activate the nuclear factor erythroid 2-related factor 2 (Nrf2), a regulator of several phase II detoxifying and antioxidant genes, such as the System Xc- subunit xCT. Here, we studied (i) the effect of the Aß fragment 25-35 (Aß25-35) on Nrf2-dependent System Xc- expression in U373 human astroglial cells and (ii) the effect of Aß25-35-induced astrocytic response on neuronal cell viability using an in vitro co-culture system. We found that Aß25-35 was able to activate an antioxidant response in astrocytes, by inducing both Nrf2 activation and System Xc- up-regulation. However, this astrocytic response caused an enhanced cell mortality of co-cultured SH-SY5Y cells, taken as a neuronal model. Consistently, the specific System Xc- inhibitor sulfasalazine prevented the increase of both neuronal mortality and extracellular glutamate levels, thus indicating that the neurotoxic effect was due to an augmented release of glutamate through the transporter. The involvement of NMDA receptor activation in this pathway was also demonstrated using the specific inhibitor MK801 that completely restored neuronal viability at the control levels. The present study sheds light on the Nrf2/system Xc- pathway in the toxicity induced by Aß25-35 and may help to better understand the involvement of astrocytes in neuronal death during Alzheimer's disease.

Transplantation of a Severely Traumatized Liver During the COVID-19 Pandemic: A Case Report and Review of the Literature.

Shortages of grafts for liver transplant remain a persistent problem. The use of lacerated livers for liver transplant can add an option for extended criteria donations, especially during the COVID-19 pandemic. We present the case of a successful liver transplant performed using a high-grade lacerated liver previously treated with superselective arterial embolization and packing for bleeding control. In view of the absence of guidelines for the use of lacerated livers for transplant, we also performed a review of the literature on injured liver grafts that were used for liver transplants. Meticulous care and careful selection of recipients were essential prerequisites for achieving successful outcomes.