The uncontrolled spread of the coronavirus disease 2019 (COVID-19) has called for unprecedented measures, to the extent that the Italian government has imposed a quarantine on the entire country. ...Quarantine has a huge impact and can cause considerable psychological strain. The present study aims to establish the prevalence of psychiatric symptoms and identify risk and protective factors for psychological distress in the general population. An online survey was administered from 18-22 March 2020 to 2766 participants. Multivariate ordinal logistic regression models were constructed to examine the associations between sociodemographic variables; personality traits; depression, anxiety, and stress. Female gender, negative affect, and detachment were associated with higher levels of depression, anxiety, and stress. Having an acquaintance infected was associated with increased levels of both depression and stress, whereas a history of stressful situations and medical problems was associated with higher levels of depression and anxiety. Finally, those with a family member infected and young person who had to work outside their domicile presented higher levels of anxiety and stress, respectively. This epidemiological picture is an important benchmark for identifying persons at greater risk of suffering from psychological distress and the results are useful for tailoring psychological interventions targeting the post-traumatic nature of the distress.
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.
•Moderate risk (Class III of TRI) shown in exposure to tested formulations ≥ 100 μg/l.•Chemical analysis on field samples revealed low Gd concentrations in freshwater.•Teratogenic Risk Index on field samples varied from high (Class IV) to low (Class I).
Recent observation identifies subendothelial (mural) cells expressing MCAM, a specific system of clonogenic, self-renewing, osteoprogenitors (a.k.a, "mesenchymal stem cells") in the microvascular ...compartment of post-natal human bone marrow (BM). In this study, we used MCAM/CD146, as a marker to localize, isolate and assay subendothelial clonogenic cells from the microvasculature of postnatal human skeletal muscle. We show here that these cells share with their BM counterpart, anatomic position (subendothelial/adventitial) and ex vivo clonogenicity (CFU-Fs). When assayed under the stringent conditions, these cells display a high spontaneous myogenic potential (independent of co-culture with myoblasts or of in vivo fusion with local myoblasts), which is otherwise only attained in cultures of satellite cells. These muscle-derived mural cells activated a myogenic program in culture. Cultured CD146+ cells expressed the myogenic factors (Pax7, Pax3 and Myf5), NCAM/CD56, desmin as well as proteins characteristic of more advanced myogenic differentiation, such as myosin heavy chain. In vivo, these cells spontaneously generate myotubes and myofibrils. These data identify the anatomy and phenotype of a novel class of committed myogenic progenitor in human post-natal skeletal muscle of subendothelial cells associated with the abluminal surface of microvascular compartment distinct from satellite cells.
In the context of legal damage evaluations, evaluees may exaggerate or simulate symptoms in an attempt to obtain greater economic compensation. To date, practitioners and researchers have focused on ...detecting malingering behavior as an exclusively unitary construct. However, we argue that there are two types of inconsistent behavior that speak to possible malingering-accentuating (i.e., exaggerating symptoms that are actually experienced) and simulating (i.e., fabricating symptoms entirely)-each with its own unique attributes; thus, it is necessary to distinguish between them. The aim of the present study was to identify objective indicators to differentiate symptom accentuators from symptom producers and consistent participants. We analyzed the Structured Inventory of Malingered Symptomatology scales and the Minnesota Multiphasic Personality Inventory-2 Restructured Form validity scales of 132 individuals with a diagnosed adjustment disorder with mixed anxiety and depressed mood who had undergone assessment for psychiatric/psychological damage. The results indicated that the SIMS Total Score, Neurologic Impairment and Low Intelligence scales and the MMPI-2-RF Infrequent Responses (F-r) and Response Bias (RBS) scales successfully discriminated among symptom accentuators, symptom producers, and consistent participants. Machine learning analysis was used to identify the most efficient parameter for classifying these three groups, recognizing the SIMS Total Score as the best indicator.
Previously, we reported that HIV-Tat elicits spermine oxidase (SMO) activity upregulation through NMDA receptor (NMDAR) stimulation in human SH-SY5Y neuroblastoma cells, thus increasing ROS ...generation, which in turn leads to GSH depletion, oxidative stress, and reduced cell viability. In several cell types, ROS can trigger an antioxidant cell response through the transcriptional induction of oxidative stress-responsive genes regulated by the nuclear factor erythroid 2-related factor 2 (Nrf2). Here, we demonstrate that Tat induces both antioxidant gene expression and Nrf2 activation in SH-SY5Y cells, mediated by SMO activity. Furthermore, NMDAR is involved in Tat-induced Nrf2 activation. These findings suggest that the NMDAR/SMO/Nrf2 pathway is an important target for protection against HIV-associated neurocognitive disorders.
Chronic oxidative stress, which occurs in brain tissues of HIV-infected patients, is involved in the pathogenesis of HIV-associated dementia. Oxidative stress can be induced by HIV-1-secreted ...proteins, either directly or indirectly through the release of cytotoxic factors. In particular, HIV-1 Tat is able to induce neuronal death by interacting with and activating the polyamine-sensitive subtype of the NMDA receptor (NMDAR). Here, we focused on the role of polyamine catabolism in Tat-induced oxidative stress in human neuroblastoma (SH-SY5Y) cells. First, Tat was found to induce reactive oxygen species production and to affect cell viability in SH-SY5Y cells, these effects being mediated by spermine oxidase (SMO). Second, Tat was observed to increase SMO activity as well as decreasing the intracellular spermine levels. Third, Tat-induced SMO activation was completely prevented by the NMDAR antagonist MK-801, clearly indicating an involvement of NMDAR stimulation. Finally, pretreatment of cells with N-acetylcysteine, a scavenger of H2O2, and with MK-801 was able to completely inhibit reactive oxygen species formation and to restore cell viability. Altogether, these data strongly suggest a role for polyamine catabolism-derived H2O2 in neurotoxicity as elicited by Tat-stimulated NMDAR.
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•The role of polyamine catabolism in Tat-induced oxidative stress was studied.•Tat induces reactive oxygen species and affects cell viability through SMO.•Tat increases SMO activity and decreases the intracellular spermine levels.•Tat-induced SMO activation is completely prevented by the NMDAR antagonist MK-801.•SMO-derived H2O2 is involved in neurotoxicity elicited by Tat-stimulated NMDAR.
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 X
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 X
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-X
upregulation, thus highlighting the mechanistic role of iron in the biological activities of the glycoprotein.
Amyloid-β (Aβ) 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 Aβ fragment 25-35 (Aβ25-35) on Nrf2-dependent System Xc− expression in U373 human astroglial cells and (ii) the effect of Aβ25-35-induced astrocytic response on neuronal cell viability using an in vitro co-culture system. We found that Aβ25-35 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 Aβ25-35 and may help to better understand the involvement of astrocytes in neuronal death during Alzheimer’s disease.
The use of machine learning (ML) models in the detection of malingering has yielded encouraging results, showing promising accuracy levels. We investigated the possible application of this ...methodology when trained on behavioral features, such as response time (RT) and time pressure, to identify faking behavior in self-report personality questionnaires. To do so, we reintroduced the article of Roma et al. (2018), which highlighted that RTs and time pressure are useful variables in the detection of faking; we then extended the number of participants and applied an ML analysis.
The sample was composed of 175 subjects, of whom all were graduates (having completed at least 17 years of instruction), male, and Caucasian. Subjects were randomly assigned to four groups: honest speeded, faking-good speeded, honest unspeeded, and faking-good unspeeded. A software version of the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) was administered.
Results indicated that ML algorithms reached very high accuracies (around 95%) in detecting malingerers when subjects are instructed to respond under time pressure. The classifiers' performance was lower when the subjects responded with no time restriction to the MMPI-2-RF items, with accuracies ranging from 75% to 85%. Further analysis demonstrated that
-scores of validity scales are ineffective to detect fakers when participants were not under temporal pressure (accuracies 55-65%), whereas temporal features resulted to be more useful (accuracies 70-75%). By contrast, temporal features and
-scores of validity scales are equally effective in detecting fakers when subjects are under time pressure (accuracies higher than 90%).
To conclude, results demonstrated that ML techniques are extremely valuable and reach high performance in detecting fakers in self-report personality questionnaires over more the traditional psychometric techniques. Validity scales MMPI-2-RF manual criteria are very poor in identifying under-reported profiles. Moreover, temporal measures are useful tools in distinguishing honest from dishonest responders, especially in a no time pressure condition. Indeed, time pressure brings out malingerers in clearer way than does no time pressure condition.
Background
Liver transplantation (LT) is a well-established procedure for hepatocellular carcinoma (HCC) within the Milan criteria. Yttrium-90 microspheres radioembolization (Y90-RE) has shown to be ...an effective and safe treatment of primary liver tumors. We retrospectively evaluate the efficacy of the Y90-RE in patients with HCC prior to LT.
Methods
From January 2002 to December 2015, 365 patients were transplanted at the San Camillo Hospital Center. One hundred forty-three patients were transplanted for HCC, and in 22 cases the patients were treated with Y90-RE before LT.
Results
Three patients were treated with Y90-RE within the Milan criteria, and 19 patients were out of criteria before Y90-RE. Four patients had an increasing MELD score between Y90-RE and LT. On the other hand, alpha-fetoprotein decreases after Y90-RE treatment in all cases. No patient death was observed in Y90-RE procedure or at LT. In 78.9 % of cases, a successful downstaging was observed, and in 100 % of cases bridging was achieved. From Y90-RE treatment overall survival was 43.9 months. From LT, overall mean survival was 30.2 months with a free survival of 29.6 months. The overall survival after LT analysis between the patients treated with Y90-RE and patients without was not significant (
p
= 0.113). Free survival analysis was not significant (
p
= 0.897) between the two populations.
Conclusions
We successfully performed LT in patients after Y90-RE treatment both as bridging and downstaging for HCC and obtained a similar overall and free survival of LT for HCC within Milan criteria. Y90-RE becomes a real option to provide curative therapy for patients who traditionally are not considered eligible for surgery.
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