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Male 12-year-old patient presenting urethrorrhagia after straddle injury associated to hemodynamic instability secondary to traumatic formation of pseudoaneurysm of the pudendal artery in the bulb of the penis. Satisfactory treatment with angiographic selective and direct percutaneous embolization was performed, with resolution of the bleeding.

Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is common after chimeric antigen receptor T-cell (CAR-T) therapy., Objective: This study aimed to assess the impact of preinfusion electroencephalography (EEG) abnormalities and EEG findings at ICANS onset for predicting ICANS risk and severity in 56 adult patients with refractory lymphoma undergoing CAR-T therapy., Study Design: EEGs were conducted at the time of lymphodepleting chemotherapy and shortly after onset of ICANS., Results: Twenty-eight (50%) patients developed ICANS at a median time of 6 days after CAR-T infusion. Abnormal preinfusion EEG was identified as a risk factor for severe ICANS (50% vs. 17%, P = 0.036). Following ICANS onset, EEG abnormalities were detected in 89% of patients [encephalopathy (n = 19, 70%) and/or interictal epileptiform discharges (IEDs) (n = 14, 52%)]. Importantly, IEDs seemed to be associated with rapid progression to higher grades of ICANS within 24 h., Conclusions: If confirmed in a large cohort of patients, these findings could establish the basis for modifying current management guidelines, enabling the identification of patients at risk of neurotoxicity, and providing support for preemptive corticosteroid use in patients with both initial grade 1 ICANS and IEDs at neurotoxicity onset, who are at risk of neurological impairment., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

In 2020, the European Commission published a regulation that states all producers of white paints containing titanium dioxide (TiO 2 ) must provide a warning label on their products. Exposure during the production and application of products containing TiO 2 can be harmful, and therefore these products must be labeled as "may cause cancer." The paint industry is a major user of TiO 2 pigment. This study focuses on pigment release from three TiO 2 -based paints and discusses the effect of paint formulation, more precisely the Pigment Volume Concentration (PVC), to predict TiO 2 pigment release from the paints during a simulated use phase and at the end of life (EoL). The use phase considered mild abrasion of painted panels that simulated cleaning or touching. The EoL phase was studied using leaching tests simulating landfill disposal. TiO 2 release during both activities was evident with a high discrepancy between the three paints. While dry rubbing was similar for all paints, activities involving water present a high release link to paint matrix degradation. The paint pigment volume concentration and the paint permeability determines the TiO 2 release during wet rubbing and leaching. This work represents an attempt to identify the paint permeability as a matrix-related parameter to predict TiO 2 release and a way to use of this parameter to develop safer products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study examined access to technology and telehealth among young adults (ages 18-24) who were court-involved and were recruited from an alternative sentencing program in New York City., Methods: Using sequential mixed methods design, we examined demographic factors linked with access to technology and perceived usefulness of the Internet among n = 321 young adults who were court-involved (75% male, 65% African American, 35% Latinx). We then conducted in-depth interviews with 27 young adults to elicit first-person account of their access to, interest in, and experience with technology and telehealth., Results: Although most participants had access to a phone with a data plan, a substantial proportion reported inconsistent access to the technology critical to telehealth. Certain young adults were more likely to lack consistent access to the technology needed for telehealth, including Black young adults, males, those with less than a high school diploma, those with a history of homelessness, and those who had difficulties paying for basic necessities. Qualitative interviews revealed that most had a strong self-efficacy using technology, while distrust of technology, inexperience with and skepticism of telehealth, low perceived need for care, and medical mistrust were common significant barriers in this underserved population., Discussion: Findings underscored the critical need to address medical mistrust and increase access to and utilization of care among young adults who are court-involved. Results can inform the development and implementation of interventions designed to improve accessibility and acceptability of telehealth., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate pathological changes in fossils from the Brazilian Intertropical Region (BIR), expanding the records of previously reported diseases for representatives of the Quaternary South American megafauna, including taxa not studied in previous works., Materials and Methods: We carried out a thorough macroscopic analysis of fifteen unpublished specimens belonging to representatives of the Quaternary megafauna of BIR to identify evidence of pathological alterations., Results: Alterations included: osteophytes in Toxodontidae, Megatheridae and E. laurillardi; rough subchondral bone, bone overgrowth and bone erosion in E. laurillardi; slit-shaped subchondral depressions in Equidae and E. laurillardi; and a triangular-shaped porous lesion in Mylodontidae., Conclusions: The alterations found allowed the recognition of the first cases of osteoarthritis for Toxodontidae and articular depressions for Equidae, and new cases of both diseases in Eremotherium laurillardi; a new case of osteochondritis dissecans for Mylodontidae; potential new cases of calcium pyrophosphate deposition and spondyloarthropathy for E. laurillardi SIGNIFICANCE: Our results provide additional evidence that calcium pyrophosphate deposition disease was widely spread among species of the South American megafauna and suggest that osteochondritis dissecans may have been relatively common among ground sloths., Limitations: The identification of calcium pyrophosphate deposition and spondyloarthropathy in E. laurillardi are quite tentative because the evidence found is ambiguous and the number of examined specimens is limited., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The plastisphere has been widely studied in the oceans; however, there is little information on how living organisms interact with the plastisphere in freshwater ecosystems, and particularly on how this interaction changes over time. We have characterized, over one year, the evolution of the eukaryotic and bacterial communities colonizing four everyday plastic items deployed in two sites of the same river with different anthropogenic impact. α-diversity analyses showed that site had a significant role in bacterial and eukaryotic diversity, with the most impacted site having higher values of the Shannon diversity index. β-diversity analyses showed that site explained most of the sample variation followed by substrate type (i.e., plastic item) and time since first colonization. In this regard, core microbiomes/biomes in each plastic at 1, 3, 6 and 12 months could be identified at genus level, giving a global overview of the evolution of the plastisphere over time. The measured concentration of antibiotics in the river water positively correlated with the abundance of antibiotic resistance genes (ARGs) on the plastics. These results provide relevant information on the temporal dynamics of the plastisphere in freshwater ecosystems and emphasize the potential contribution of plastic items to the global spread of antibiotic resistance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Amid concerns on the myriad of existing chemical stressors in agroecosystems, pesticides and particularly neonicotinoid insecticides are in the forefront. Despite that, these neurotoxic compounds remain the dominant group of insecticides in worldwide use with the added versatility of use in seed coatings. Such use sparks environmental concerns counterbalanced by their reported insecticidal efficacy and potential plant bioactivation. Nonetheless, this alleged double benefit and interconnection expected with neonicotinoids has been little explored particularly when the whole plant phenology is considered. Regardless of the expected efficacy against targeted insect pest species, like whiteflies, neonicotinoids may spark dual effect on plants - negative at higher concentrations, positive at low concentrations, which is consistent with the hormesis phenomenon that may be expressed as a plant bioactivation. This effect may also cascade to the targeted insect species, what deserves attention. Therefore, soybean seeds treated with increasing concentrations of the neonicotinoid thiamethoxam were followed throughout their development in greenhouse, recording the plant response and yield, besides their effect in whiteflies (Bemisia tabaci MEAM1). Thiamethoxam application was correlated to leaf contents of thiamethoxam and its metabolite clothianidin. Plant hormesis was found for leaf area and root growth, but not for other plant morphological or physiological parameters, nor plant yield. The insecticide concentration-dependency compromised whitefly population growth without evidence of cascading any plant-mediated hormesis to the insects. Thus, although plant hormesis was recognized with thiamethoxam in treated soybean seeds in relevant parameters, no evidence of plant bioactivation was observed to justify its use with such a secondary objective, nor did this hormesis impair whitefly control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to determine and evaluate the postvaccination variation in immunoglobulin G (IgG) receptor-binding domain (RBD) produced in non-SARS-CoV-2-infected patients with nephropathy and renal replacement therapy., Methods: This is a follow-up study of the humoral response to the BNT162b2 messenger ribonucleic acid COVID-19 vaccine in patients with nephropathy, comparing it with itself at different times and with the healthy population., Results: In patients with nephropathy, a very striking decrease in IgG RBD was observed compared with the healthy population (P<0.001) at three months after the second dose. In patients with nephropathy, the response rate ≥590 binding antibody units/ml (4154 AU/ml) was detected in 45% of patients, 15 days after the second dose, whereas at 3 months, this decreased to 9% (P<0.05) and then increased to 86% after the third dose (P<0.001)., Conclusion: In patients with nephropathy and renal replacement therapy, it is necessary to administer a third-dose vaccination within 3 months after the second dose. It is important to continue monitoring the humoral response to obtain a better SARS-CoV-2 vaccination schedule., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this work, a solar electrochemical-raceway pond reactor (SEC-RPR) is used to treat textile industrial wastewater by solar photoelectron-Fenton (SPEF) at pilot plant scale for the first time. The SEC-RPR is composed of an electrochemical filter press-cell coupled to RPR, where H 2 O 2 is electro-generated. A complete study about experimental variables such as current, catalyst concentration, pollutant load or liquid depth is conducted based on methyl orange removal, mineralization and decolorization. Validation of the SPEF process using SEC-RPR reached more than 80% of mineralization, as well as the complete decolorization of the solution. The good performance of the SPEF treatment in the new SEC-RPR led to quick degradation kinetics, mainly due to the synergetic action of solar radiation and good distribution of H 2 O 2 electrogenerated in the photoreactor. 100% Methyl Orange degradation was achieved after 150, 60, 45, 30 and 20 min of reaction time applying current density equal to 5, 10, 20, 40 and 60 mA cm -2 , respectively. However, the increase of current density decreased the mineralization current efficiency. Up to 10 aromatics intermediates and 5 short-chain carboxylic acids were identified by LC-MS and HPLC analysis and a reaction pathway for MO mineralization by SPEF is proposed. This study represents an essential preliminary step towards the development of the first SEC-RPR at demo scale., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Abnormalities in Ca 2+ homeostasis in Bipolar Disorders (BD) have been associated with impairments in glutamatergic receptors and voltage-gated calcium channels. Increased anterior cingulate cortex (ACC) glutamatergic neurometabolites have been consistently disclosed in BD by proton magnetic resonance spectroscopy ( 1 H-MRS). A single nucleotide polymorphism (SNP) in the CACNA1C gene (rs1006737), which encodes the alpha 1-C subunit of the L-type calcium channel, has been associated with BD and is reported to modulate intra-cellular Ca 2+ . Thus, this study aimed to explore the association of the CACNA1C genotype with ACC glutamatergic metabolites measured by 1 H-MRS in both BD and HC subjects. A total of 194 subjects (121 euthymic BD type I patients and 73 healthy controls (HC) were genotyped for CACNA1C rs1006737, underwent a 3-Tesla 1 H-MRS imaging examination and ACC glutamatergic metabolite were assessed. We found overall increased glutamatergic metabolites in AA carriers in BD. Specifically, higher Glx/Cr was observed in subjects with the AA genotype compared to both AG and GG in the overall sample (BD + HC). Also, female individuals in the BD group with AA genotype were found to have higher Glx/Cr compared to those with other genotypes. CACNA1C AA carriers in use of anticonvulsant medication had higher estimated Glutamine (Glx-Glu) than the other genotypes. Thus, this study suggest an association between calcium channel genetics and increased glutamatergic metabolites in BD, possibly playing a synergic role in intracellular Ca 2+ overload and excitotoxicity., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2022. Published by Elsevier B.V.)

Current knowledge on the capacity of plastics as vectors of microorganisms and their ability to transfer microorganisms between different habitats (i.e. air, soil and river) is limited. The objective of this study was to characterise the evolution of the bacterial community adhered to environmental plastics [low-density polyethylene (LDPE)] across different environments from their point of use to their receiving environment destination in the sea. The study took place in a typical Mediterranean intermittent river basin in Larnaka, Cyprus, characterised by a large greenhouse area whose plastic debris may end up in the sea due to mismanagement. Five locations were selected to represent the environmental fate of greenhouse plastics from their use, through their abandonment in soil and subsequent transport to the river and the sea, taking samples of plastics and the surrounding environments (soil and water). The bacterial community associated with each sample was studied by 16S rRNA metabarcoding; also, the main physicochemical parameters in each environmental compartment were analysed to understand these changes. The identification and chemical changes in greenhouse plastics were tracked using Attenuated Total Reflection Fourier Transform Infra-red spectroscopy (ATR-FTIR). Scanning Electron Microscope (SEM) analysis demonstrated an evolution of the biofilm at each sampling location. β-diversity studies showed that the bacterial community adhered to plastics was significantly different from that of the surrounding environment only in samples taken from aqueous environments (freshwater and sea) (p-value p-value > 0.05). The environmental parameters (pH, salinity, total nitrogen and total phosphorus) explained the differences observed at each location to a limited extent. Furthermore, bacterial community differences among samples were lower in plastics collected from the soil than in plastics taken from rivers and seawater. Six genera (Flavobacterium, Altererythrobacter, Acinetobacter, Pleurocapsa, Georgfuchsia and Rhodococcus) were detected in the plastic, irrespective of the sampling location, confirming that greenhouse plastics can act as possible vectors of microorganisms between different environments: from their point of use, through a river system to the final coastal receiving environment. In conclusion, this study confirms the ability of greenhouse plastics to transport bacteria, including pathogens, between different environments. Future studies should evaluate these risks by performing complete sequencing metagenomics to decipher the functions of the plastisphere., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The fluorescent properties of cadmium telluride (CdTe) containing quantum dots (QDs) have led to novel products and applications in the ink and pigment industry. The toxic effects of the emissions associated to the use of printing ink containing CdTe QDs might differ from those of conventional formulations which do not integrate nanoparticles, as CdTe QDs might be emitted. Within this work, the airborne emissions of a water-soluble fluorescent ink containing polyethylene glycol (PEG)-coated CdTe QDs of 3-5 nm diameter have been characterized and studied under controlled conditions during household inkjet printing in a scenario simulating the use phase. Subsequently, the cytotoxicological potential of atomized CdTe QDs ink in an acute exposure regimen simulating an accidental, worse-case scenario has been evaluated in vitro at the air-liquid interface (ALI) using the pulmonary cell line BEAS-2B. Endpoints screened included cell viability, oxidative stress and inflammatory effects. We have observed that CdTe QDs ink at 54.7 ng/mL decreased cell viability by 25.6 % when compared with clean air after 1h of exposure; a concentration about 65 times higher was needed to observe a similar effect in submerged conditions. However, we did not observe oxidative stress or inflammatory effects. The present study integrates the development of scenarios simulating the use phase of nano-additivated inks and the direct cell exposure for in vitro effects assessment, thus implementing a life-cycle oriented approach in the assessment of the toxicity of CdTe QDs., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021. Published by Elsevier B.V.)

Microbial colonization of microplastics (MPs) in aquatic ecosystems is a well-known phenomenon; however, there is insufficient knowledge of the early colonization phase. Wastewater treatment plant (WWTP) effluents have been proposed as important pathways for MPs entry and transport in aquatic environments and are hotspots of bacterial pathogens and antibiotic resistance genes (ARGs). This study aimed at characterizing bacterial communities in the early stage of biofilm formation on seven different types of MPs deployed in two different WWTPs effluents as well as measuring the relative abundance of two ARGs (sulI and tetM) on the tested MPs. Illumina Miseq sequencing of the 16S rRNA showed significant higher diversity of bacteria on MPs in comparison with free-living bacteria in the WWTP effluents. β-diversity analysis showed that the in situ environment (sampling site) and hydrophobicity, to a lesser extent, had a role in the early bacterial colonization phase. An early colonization phase MPs-core microbiome could be identified. Furthermore, specific core microbiomes for each type of polymer suggested that each type might select early attachment of bacteria. Although the tested WWTP effluent waters contained antibiotic resistant bacteria (ARBs) harboring the sulI and tetM ARGs, MPs concentrated ARBs harboring the sulI gene but not tetM. These results highlight the relevance of the early attachment phase in the development of bacterial biofilms on different types of MP polymers and the role that different types of polymers might have facilitating the attachment of specific bacteria, some of which might carry ARGs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cryopreservation of gametes, embryos and larvae of marine invertebrates has been investigated in many studies throughout the years. There are many favorable studies on sperm cryopreservation but oocytes are still under research as no successful results have been sustainably obtained for this type of cells. The preservation of both maternal and paternal gametes separately would provide a reliable source of genetic material for their application to conservation, aquaculture and fundamental research. Unfortunately to date, it has not been possible to cryopreserve eggs from marine organisms. The aim of this review is to go over the factors that have been historically considered as obstacles for oocyte cryopreservation in aquatic organisms and discern those that may specifically apply to eggs of the sea urchin Paracentrotus lividus., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The objective of this study was to evaluate an investigative model which encompassed the risk factors, incidence, timing and causes of perinatal mortality (PM) (0-48 h) on high risk dairy farms (PM of >5% in the previous year) in Switzerland. This pilot-study was carried out on 47 predominantly Holstein PM calves from 21 dairy farms, between September 2016 and January 2018. Gross pathological examinations of calves and placentae as well as histopathological examinations of internal organs and placental tissue were performed. Further investigations included microbiological examinations: broad-spectrum bacterial and fungal culture, detection of Chlamydia abortus, Coxiella burnetii, pathogenic Leptospira spp. and Neospora caninum by real-time PCR (qPCR) and of bovine viral diarrhoea virus (BVDV) by Ag-ELISA. Maternal blood samples were used for serology of bovine herpesvirus 1 (BHV-1), Brucella abortus, Chlamydia abortus, Coxiella burnetii and nine pathogenic leptospiral serovars and the evaluation of trace element status. A questionnaire was completed with the farmer, which included general farm characteristics and case-related data. Inbreeding coefficients (IC) were calculated for pure-bred matings. At the farm-level, the PM rate was 10.0% (5.3-28.2%) and at the cow-level, 11.5%. These values, from high-risk farms, were approximately five-times higher than the contemporary national bovine PM rate (2.3%) in Switzerland. The risk factors associated with these high PM rates were the self-selection of high risk herds, the high proportion of primiparae in these herds (45%) and the evidence of widespread pathogenic infections on these farms (exposure: 67% of herds, 53% of dams; infection: 57% of herds, 45% of calves). The majority (68.1%) of calves died intrapartum. The most commonly diagnosed initiating/ultimate cause of death (UCOD) was infection (34%) of which Coxiella burnetii was the most frequently detected pathogen, by antigen. The most frequently diagnosed proximate cause of death (PCOD) was asphyxia (44.7%), though multiple PCOD was also common (21.3%). This study was the first detailed investigation of bovine PM in Switzerland. Infectious causes were diagnosed more frequently than expected. While the findings from these high PM Swiss herds may have limited external validity, the investigative model adopted and the detailed research methodologies employed can be replicated and re-evaluated, respectively, in future studies on PM internationally., Competing Interests: Declaration of competing interest All authors rule out any conflict of interest regarding this work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The objective of this work was to investigate the effects of salinized water on Lippia gracilis by determining the ion accumulation capacity and morphophysiological changes as a function of salinity and time of exposure to stress. L. gracilis was irrigated with water containing different concentrations of salts and electrical conductivities. The analyses were conducted 25 and 50 days after stress (DAS), in leaf, stem/branches, and roots. Plant height (Hplants), basal stem diameter (Φstem), and mean unitary leaf area (ULA) were determined. After that, the plant material was dried, and the total dry biomass (TDB) (in g plant -1 ), leaf dry biomass (LDB), stem dry biomass (SDB), and the roots dry biomass (RDB) were determined. Based on these data, the following variables were calculated: total leaf area (TLA) in cm 2 plant -1 ; biomass allocation fraction (BAF) obtained by dividing the biomass of the stem, leaves, and roots, separately, with the total plant biomass; relative growth rate (RGR); net assimilation rate (NAR); leaf area ratio (LAR); specific leaf area (SLA); and sclerophylly index (SI). The concentrations of potassium and sodium ions were quantified by atomic absorption spectrophotometry and the chloride ion concentration was determined by argentometric titration. L. gracilis showed a variable response to salt stress as a function of time, having a considerable capacity to withstand an increasing load of toxic ions, while maintaining a positive growth rate, highlighting the potential use of the species in moderately saline environments., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Good water quality for livestock is essential for animal health, supply of safe food and food production economy. Few countries have established water quality criteria for livestock for chemical contaminants. For those that have them, the values are quite variable among each other for the same substance due to differences in the approach for the acceptable daily intakes and algorithms for the calculation. In several countries, including Brazil, these standards are based on international or other countries' data, which differ among protected species, exposure scenarios, and levels of protection. The objective of this work was to discuss critical issues to establish chemical water quality criteria for livestock in Brazil. A discussion about the difficulties involved and the alternatives when sufficient data are not available is presented. Using the Canadian framework for reference, we provide recommendations on a revised framework and alternatives regarding the use of chronic studies as mandatory, defaulting to human health drinking water quality guidelines/criteria for livestock, the use of additional safety factors, and alternatives in the absence of toxicological data., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This work studied the accumulation of plastic debris in a remote beach located in La Graciosa island (Chinijo archipelago, Canary Islands). Microplastics were sampled in the 1-5 mm mesh opening range. An average plastic density of 36.3 g/m 2 was obtained with a large variability along the 90 m of the beach (from 8.5 g/m 2 to 103.4 g/m 2 ). Microplastic particles preferentially accumulated in the part of the beach protected by rocks. A total number of 9149 plastic particles were collected, recorded and measured, 87% of which corresponded to fragments. Clear colours and microscopic evidence of weathering corresponded to aged plastics wind-driven by the surface Canary Current. The chemical composition of plastics particles corresponded to PE (63%), PP (32%) and PS (3%). Higher PE/PP ratios were recorded in the more protected parts of the beach, suggesting preferential accumulation of more aged fragments., (Copyright © 2019. Published by Elsevier Ltd.)

Pathological α-synuclein (α-syn) overexpression and iron (Fe)-induced oxidative stress (OS) are involved in the death of dopaminergic neurons in Parkinson's disease (PD). We have previously characterized the role of triacylglycerol (TAG) formation in the neuronal response to Fe-induced OS. In this work we characterize the role of the α-syn variant A53T during Fe-induced injury and investigate whether lipid metabolism has implications for neuronal fate. To this end, we used the N27 dopaminergic neuronal cell line either untransfected (UT) or stably transfected with pcDNA3 vector (as a transfection control) or pcDNA-A53T-α-syn (A53T α-syn). The overexpression of A53T α-syn triggered an increase in TAG content mainly due to the activation of Acyl-CoA synthetase. Since fatty acid (FA) β-oxidation and phospholipid content did not change in A53T α-syn cells, the unique consequence of the increase in FA-CoA derivatives was their acylation in TAG moieties. Control cells exposed to Fe-induced injury displayed increased OS markers and TAG content. Intriguingly, Fe exposure in A53T α-syn cells promoted a decrease in OS markers accompanied by α-syn aggregation and elevated TAG content. We report here new evidence of a differential role played by A53T α-syn in neuronal lipid metabolism as related to the neuronal response to OS., (Copyright © 2018. Published by Elsevier Inc.)

Background: Adjuvant chemotherapy is controversial in patients with locally advanced rectal cancer after preoperative chemoradiation. Valentini et al developed 3 nomograms (VN) to predict outcomes in these patients. The neoadjuvant rectal score (NAR) was developed after VN to predict survival. We aimed to validate these tools in a retrospective cohort at an academic institution., Patients and Methods: VN and the NAR were applied to 158 consecutive patients with locally advanced rectal cancer treated with chemoradiation followed by surgery. According to the score, they were divided into low, intermediate, or high risk of relapse or death. For statistical analysis, we performed Kaplan-Meier curves, log-rank tests, and Cox regression analysis., Results: Five-year overall survival was 83%, 77%, and 67% for low-, intermediate-, and high-risk groups, respectively (P = .023), according to VN, and 84%, 71%, and 59% for low-, intermediate-, and high-risk groups, respectively (P = .004), according to NAR. When the score was considered as a continuous variable, a significant association with the risk of death was observed (NAR: hazard ratio, 1.04; P < .001; VN: hazard ratio, 1.10; P < .001)., Conclusion: We confirmed the value of these scores to stratify patients according to their individual risk when designing new trials., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We have previously shown that phospholipase D (PLD) pathways have a role in neuronal degeneration; in particular, we found that PLD activation is associated with synaptic injury induced by oxidative stress. In the present study, we investigated the effect of α-synuclein (α-syn) overexpression on PLD signaling. Wild Type (WT) α-syn was found to trigger the inhibition of PLD1 expression as well as a decrease in ERK1/2 phosphorylation and expression levels. Moreover, ERK1/2 subcellular localization was shown to be modulated by WT α-syn in a PLD1-dependent manner. Indeed, PLD1 inhibition was found to alter the neurofilament network and F-actin distribution regardless of the presence of WT α-syn. In line with this, neuroblastoma cells expressing WT α-syn exhibited a degenerative-like phenotype characterized by a marked reduction in neurofilament light subunit (NFL) expression and the rearrangement of the F-actin organization, compared with either the untransfected or the empty vector-transfected cells. The gain of function of PLD1 through the overexpression of its active form had the effect of restoring NFL expression in WT α-syn neurons. Taken together, our findings reveal an unforeseen role for α-syn in PLD regulation: PLD1 downregulation may constitute an early mechanism in the initial stages of WT α-syn-triggered neurodegeneration., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Using the case of synthetic cathinones (commonly referred to as 'bath salts' in the US context), this paper analyses structural factors surrounding novel psychoactive substances (NPS) as contributing to the unique risk environment surrounding their use. Drawing on interviews with 39 people who use bath salts from four U.S. cities and analysis of the infrastructural, social, economic, and policy contexts, we document the unique harms related to changing contexts for illicit drug regulation, manufacture, and consumption. Findings suggest that NPS and designer drug markets, which are highly reliant upon the internet, share characteristics of the entertainment industry which has come to rely more heavily upon profits derived from the 'long tail' of myriad lesser-known products and the diminished centrality of 'superstars' and 'hits'. Findings point toward increased theoretical and policy attention to changing drug market structures, more rigorous evaluations of drug 'analogues' legislation and greater involvement with NPS education and testing by harm reduction agencies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Synthesized iron oxide nanoparticles have been proposed as an alternative to non-dispersed iron oxides for in situ environmental remediation. Their colloidal properties enable their injection into porous media, i.e. soils and aquifers, and offer a higher efficiency in removing contaminants. However, this dispersed state is also the cause of concerns over their environmental fate and toxicity, e.g., by increasing the exposure time to aquatic organisms in groundwater remediation activities. Therefore, the objective of in situ groundwater remediation is to establish local reactive barriers in the subsurface by injection by means of reactive colloids with a controllable mobility under in situ conditions and present as colloids as shortly as possible. In this work, we examined the toxicity of humic acid-coated colloidal goethite nanoparticles in Daphnia magna. The adaptation of the ecotoxicological standard tests for nanomaterials is intensely discussed to increase comparability and reliability of results. In the present study, the effect of different exposure conditions on goethite nanoparticles colloidal behaviour and acute Daphnia immobilization effects was investigated. For this purpose, iron concentration in the water column, aggregation state and acute effects were studied in: i) a standard test, ii) test design with exposure dispersions incubated for a week and iii) water accommodated fraction. Despite the different aggregation and settling of the particles found between the approaches tested, no differences in toxicity were observed. Coated nanoparticles were found clogging up the filtering apparatus, and/or adhered to the exoskeleton, hindering the swimming and molting, and causing the immobilization and death of the organisms at doses of ≥943mg/L (EC50). The data suggests that the toxic potential of these nanoparticles is mainly related to the physical interaction with the daphnids., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Venous thrombosis of pancreas transplant allografts often leads to graft loss. It is an worrisome complication and difficult to treat, forming the most common nonimmunological cause of graft loss. Multiple risk factors have been implicated in the development of venous thrombosis of pancreas transplant. Color Doppler ultrasonography enables early diagnosis of venous thrombosis, thus increasing the possibility of graft-rescue treatments. Endovascular management of pancreatic transplant vascular complications is scant and in the form of case reports. We report a case of early detection of pancreatic graft venous thrombosis that was treated successfully by catheter-directed thrombolysis mechanical thrombectomy, percutaneous transluminal angioplasty, and stenting of portal vein., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This work aimed to determine the chemical fingerprint of hydroethanolic extract of leaves of Caryocar coriaceum (HELCC) and the gastroprotective activity. The chemical fingerprint of HELCC was analyzed by HPLC-DAD, to quantify total phenols and flavonoids were carried out by Folin-Ciocalteu reagent and aluminum chloride assay, while in vitro antioxidant activity was evaluated by the DPPH method. The methods used to determine pharmacological activity were: gastroprotective screening test in classical models of induced acute and chronic gastric lesions and physical barrier test. Further assays were performed to demonstrate the involvement of NO, prostaglandins, ATP-dependent potassium channels, TRPV, noradrenergic α2 receptors, histamines, and opioids. The DPPH method demonstrated the antioxidant activity of the extract, in vitro, explained by the presence of polyphenols and flavonoids. Oral administration of the extract, previously dissolved in deionized water, at a dose of 100 mg/kg decreased the lesions induced by indomethacin, acidified ethanol, ethanol and acetic acid by 75.0, 72.8, 69.4 and 86.2% respectively. It was demonstrated that opioid receptors, α 2 -adrenergic receptors and primary afferent neurons sensitive to capsaicin were involved in the mechanism of gastric protection, in addition to the contribution of NO and prostaglandins. The results show that extract is a promising candidate for the treatment of gastric ulcers., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

In the current paper, a new strategy for risk assessment of nanomaterials is described, which builds upon previous project outcomes and is developed within the FP7 NANoREG project. NANoREG has the aim to develop, for the long term, new testing strategies adapted to a high number of nanomaterials where many factors can affect their environmental and health impact. In the proposed risk assessment strategy, approaches for (Quantitative) Structure Activity Relationships ((Q)SARs), grouping and read-across are integrated and expanded to guide the user how to prioritise those nanomaterial applications that may lead to high risks for human health. Furthermore, those aspects of exposure, kinetics and hazard assessment that are most likely to be influenced by the nanospecific properties of the material under assessment are identified. These aspects are summarised in six elements, which play a key role in the strategy: exposure potential, dissolution, nanomaterial transformation, accumulation, genotoxicity and immunotoxicity. With the current approach it is possible to identify those situations where the use of nanospecific grouping, read-across and (Q)SAR tools is likely to become feasible in the future, and to point towards the generation of the type of data that is needed for scientific justification, which may lead to regulatory acceptance of nanospecific applications of these tools., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD) is still incompletely understood. Several nuclear receptors play a role in liver lipid metabolism and can promote hepatosteatosis, but the possible role of vitamin D receptor (VDR) in NAFLD has not been investigated., Methods: The expression of liver VDR was investigated in apolipoprotein E knockout (apoE(-/-)) mice on a high fat diet, in wild-type mice on methionine and choline deficient diet and in NAFLD patients with hepatosteatosis and non-alcoholic steatohepatitis. The relevance of VDR was assessed in apoE(-/-) mice by deletion of VDR or paricalcitol treatment and in human HepG2 cells by VDR transfection or silencing. The role of VDR in fibrosis was also determined in VDR knockout mice (VDR(-/-)) treated with thioacetamide., Results: Expression of liver VDR was markedly induced in two mouse models of NAFLD, as well as in patients with hepatosteatosis, but decreased in non-alcoholic steatohepatitis. VDR deletion in high fat diet-fed apoE(-/-) mice protected against fatty liver, dyslipidemia and insulin resistance, and caused a decrease in taurine-conjugated bile acids, but did not influence fibrosis by thioacetamide. apoE(-/-)VDR(-/-) mouse livers showed decreased gene expression of CD36, DGAT2, C/EBPα and FGF21, and increased expression of PNPLA2, LIPIN1 and PGC1α. Treatment of apoE(-/-) mice on high fat diet with paricalcitol had modest opposite effects on steatosis and gene expression. Finally, this set of genes showed concordant responses when VDR was overexpressed or silenced in HepG2 cells., Conclusions: Induced hepatocyte VDR in NAFLD regulates key hepatic lipid metabolism genes and promotes high fat diet-associated liver steatosis. Therapeutic inhibition of liver VDR may reverse steatosis in early NAFLD., Lay Summary: The amount of vitamin D receptor is induced early in the livers of mice and humans when they develop non-alcoholic fatty liver disease. If the gene for the vitamin D receptor is deleted, hepatic lipid metabolism changes and mice do not accumulate fat in the liver. We conclude that the vitamin D receptor can contribute to the fatty liver disease promoted by a high fat diet., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Study Objective: Mesh erosion through the vagina is the most common complication of synthetic mesh used for pelvic organ prolapse repair. However, conventional transvaginal mesh excision has many technical limitations. We aimed at creating and describing a new surgical technique for transvaginal removal of exposed mesh that would enable better exposition and access, thus facilitating optimal treatment., Design: A step-by-step video showing the technique., Setting: A university tertiary care hospital., Patients: Five patients previously submitted to pelvic organ prolapse repair using synthetic mesh, presenting mesh erosion through the vagina., Interventions: Mesh excision using a laparoscopy-like operative vaginoscopy in which standard laparoscopic instruments are used through a single-incision laparoscopic surgery port device placed in the vagina., Measurements and Main Results: In all cases, a very good exposure of the mesh was achieved, a minimal tissue traction was required, and the procedures were performed in a very ergonomic way. All the patients were discharged on the same day of the surgery and had a painless postoperative course. So far, there have been no cases of relapse., Conclusion: This seems to be a simple, cheap, and valuable minimally invasive technique with many advantages in comparison with the conventional approach. More cases and time are necessary to access its long-term efficacy. It may possibly be used for the management of other conditions., (Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.)

Large efforts are invested on the development of in vitro tests to evaluate nanomaterial (NM) toxicity. In order to assess the relevance of the adverse effects identified in in vitro toxicity tests a thorough understanding of the biokinetics of NMs is critical. We used different in vitro and in vivo test methods to evaluate cell uptake and oral absorption of titanium dioxide nanoparticles (TiO2 NPs). These NPs were readily uptaken by A549 cells (carcinomic human alveolar basal epithelial cells) in vitro. Such rapid uptake contrasted with a very low oral absorption in a differentiated Caco-2 monolayer system (human epithelial colorectal adenocarcinoma cells) and after oral gavage administration to rats. In this oral study, no significant increase in the levels of titanium was recorded by ICP-MS in any of the tissues evaluated (including among other: small intestine, Peyer's patches, mesenteric lymph nodes, liver, and spleen). No NPs were observed by TEM in sections of the small intestine, except for several particles in the cytoplasm of a cell from a Peyer's Patch area. The observation of NPs in Peyer's Patch suggests that the Caco-2 monolayer system is likely to underestimate the potential for oral absorption of NPs and that the model could be improved by including M-cells in co-culture., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To assess the impact of a nutrition and oral care training program on nursing home (NH) policies and residents., Design: Cross-sectional surveys before/after intervention., Participants: One hundred thirty-eight NHs participated in the initial training., Intervention: Training sessions for staff, director, and medical practitioners for nutritional and oral care in NH., Measurements: Two waves of self-assessments over a 6- to 8-month interval described NH policies (Institution questionnaire), quality of care in newly admitted residents (Admission questionnaire), and in those present for more than 6 months (Stay questionnaire)., Results: Questionnaires were completed at both waves in 24 NHs (17.8%) for Institution, in 42 NHs including 646 residents for Admission, and in 34 NHs including 287 residents for Stay. There was no significant difference in bed capacity and resident dependency between NHs, which performed both assessments, and nonresponders. No change was observed for Institution. Malnutrition screening was carried out in almost all residents. Two risk factors were better screened after training: pressure ulcers (39.4% to 49.1%, P = .014) and dysphagia (33.5% to 41.0%, P = .049). Oral examination improved quantitatively (38.5% of residents to 48.5%) and qualitatively: risk factors for malnutrition and dysphagia were better sought (loss of posterior teeth (P < .0001), asialia (P < .0001), and candidosis (P = .002)). Similar improvements were seen in Stay assessments. Actions to counteract weight loss or low dietary intake records were not found in one third of resident records., Conclusions: Training program improved staff knowledge with positive results at the level of residents but no significant changes were seen within NH policies., (Copyright © 2014 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: The "July effect" is a widely discussed phenomenon of worse patient outcomes at teaching hospitals in July due to inexperienced house staff., Methods: We conducted a retrospective review of Organ Procurement and Transplantation Network data from Oct 1, 1987 to June 30, 2011, including longitudinal censored data of 360,330 transplantations. Demographic and comorbid variables for donors and recipients were collected. Primary outcomes were graft loss, patient death, and delayed graft function. Secondary outcomes were surgical complications, length of stay, and graft rejection. We compared survival indicators (1-month, 1-, 3-, and 5-year survival and median survival times) for both grafts and patients. We also analyzed death-censored graft survival., Results: There were fewer July donors with diabetes (p = 0.003), hypertension (p = 0.000), and extended criteria (p<0.0001). Graft survival (p = 0.000), death-censored graft survival (p = 0.001), and patient survival (p = 0.002) were statistically higher in July. After adjusting the Cox model for extended criteria donors, there was no difference in outcomes (p>0.05 for graft, death-censored graft survival, and patient survival)., Conclusion: We conclude that there is no July effect. Initially identified, superior outcomes in July may be attributed to more conservative allografts selection in the beginning of the academic year., (Copyright © 2013 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To report 4 cases of posterior scleritis with unusually unremarkable ultrasonography findings in which diagnosis was based on magnetic resonance imaging (MRI) examination., Design: Retrospective noncomparative case series., Participants: Four patients., Methods: Patients suffering from suspected posterior scleritis and previously misdiagnosed with a range of conditions after an unremarkable B-scan ultrasonography. A new and thorough review of systems, including MRI examination of the eye/orbit, was carried out., Results: All included patients were diagnosed with posterior scleritis based on MRI findings. Systemic treatment with immunosuppressors (2 patients), antibiotics (1 patient), or no treatment (1 patient) got their inflammatory condition under control., Conclusions: MRI may play a potential role in the diagnosis of posterior scleritis particularly in those clinically suspicious cases with nondefinitive ultrasonography. Further studies on this matter are warranted., (Copyright © 2011 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

In this work, the time-dependent conjugation process between a thiolated molecule (with anti-parkinsonian properties) and gold nanoparticles has been monitored and studied by the combined use of fast acquisition Ultra Violet-Visible (UV-Vis) spectra and the ability of Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) technique. From the highly informative kinetic profiles obtained it was possible to extract quantitative and qualitative information of the conjugation process which includes i) time-dependent concentration profiles and pure spectra of species involved on conjugation process, ii) estimation of molecule concentration necessary for the completeness of the conjugation reaction, iii) molecule footprint and iv) free energy of molecule adsorption., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: This was an open-label, nonrandomized, multicenter, 2-stage phase I trial of safety and preliminary efficacy of nonpegylated liposomal doxorubicin (NLD) in combination with trastuzumab in advanced breast cancer, with emphasis on cardiac toxicity., Patients and Methods: Forty patients (median age, 48 years; range, 30-74 years) with HER2/neu 2+ or 3+ tumors (by immunohistochemistry) were recruited December 1999 to November 2002. Patients were eligible if they received or= 1 cycle. Cardiac safety was assessed after completing >or= 4 full treatment cycles., Results: Thirty out of 40 patients (75%) received >or= 4 treatment cycles and were evaluable for cardiac safety. Five patients (13%), 4 who were doxorubicin pretreated, developed left ventricular ejection fraction reductions to < 50%, and 2 (5%) of these patients experienced clinical cardiac toxicity. Fifty percent of the patients had objective tumor responses; median progression-free survival was approximately 21 weeks. Twenty-six patients (65%) had grade 3/4 neutropenia; 2 patients experienced febrile neutropenia., Conclusion: Nonpegylated liposomal doxorubicin plus trastuzumab is active in HER2-positive patients with advanced breast cancer and is associated with a lower risk of cardiac toxicity than conventional doxorubicin plus trastuzumab.

Background/aims: The hepatitis C virus (HCV) structural core and non-structural NS5A proteins induce in liver cells a series of intracellular events, including elevation of reactive oxygen and nitrogen species (ROS/RNS). Since oxidative stress is associated to altered intracellular Ca(2+) homeostasis, we aimed to investigate the effect of these proteins on Ca(2+) mobilization in human hepatocyte-derived transfected cells, and the protective effect of quercetin treatment., Methods: Ca(2+) mobilization and actin reorganization were determined by spectrofluorimetry. Production of ROS/RNS was determined by flow cytometry., Results: Cells transfected with NS5A and core proteins showed enhanced ROS/RNS production and resting cytosolic Ca(2+) concentration, and reduced Ca(2+) concentration into the stores. Phenylephrine-evoked Ca(2+) release, Ca(2+) entry and extrusion by the plasma membrane Ca(2+)-ATPase were significantly reduced in transfected cells. Similar effects were observed in cytokine-activated cells. Phenylephrine-evoked actin reorganization was reduced in the presence of core and NS5A proteins. These effects were significantly prevented by quercetin. Altered Ca(2+) mobilization and increased calpain activation were observed in replicon-containing cells., Conclusions: NS5A and core proteins induce oxidative stress-mediated Ca(2+) homeostasis alterations in human hepatocyte-derived cells, which might underlie the effects of both proteins in the pathogenesis of liver disorders associated to HCV infection.

The objective of this study was to verify the possible inclusion of the Salmonella/microsome mutagenicity assay in a groundwater monitoring program as a complementary assay to assess water quality. Groundwater samples belonging to seven wells from different types of aquifers were analyzed. Three different methods for sample preparation were used: membrane filtration; liquid-liquid and XAD-4 extraction. The filtered samples were tested using TA98, TA100, YG1041 and YG1042 and the water extracts only with TA98 and TA100. No mutagenic activity was observed in any of the 16 filtered samples tested. Out of the 10 samples analyzed using XAD-4 extraction, five showed mutagenic activity with potency ranging from 130 to 1500 revertants/L. Concerning the liquid-liquid extraction, from the 11 samples analyzed, 3 showed mutagenicity. The XAD-4 extraction was the most suitable sample preparation. TA98 without S9 was found to be the most sensitive testing condition. The wells presenting water samples with mutagenic activity belonged to unconfined aquifers, which are more vulnerable to contamination. The data suggest that Salmonella/microsome assay can be used as an efficient screening tool to monitor groundwater for mutagenic activity.

There is a lack of universally accepted clinical parameters to guide the utilization of donation after cardiac death (DCD) donor livers and it is unclear as to which patients would benefit most from these organs. We reviewed our experience in 141 patients who underwent liver transplantation using DCD allografts from 1993 to 2007. Patient outcomes were analyzed in comparison to a matched cohort of 282 patients who received livers from donation after brain death (DBD) donors. Patient survival was similar, but 1-, 5- and 10-year graft survival was significantly lower in DCD (69%, 56%, 44%) versus DBD (82%, 73%, 63%) subjects (p < 0.0001). Primary nonfunction and biliary complications were more common in DCD patients, accounting for 67% of early graft failures. A donor warm ischemia time >20 min, cold ischemia time >8 h and donor age >60 were associated with poorer DCD outcomes. There was a lack of survival benefit in DCD livers utilized in patients with model for end-stage liver disease (MELD) < or =30 or those not on organ-perfusion support, as graft survival was significantly lower compared to DBD patients. However, DCD and DBD subjects transplanted with MELD >30 or on organ-perfusion support had similar graft survival, suggesting a potentially greater benefit of DCD livers in critically ill patients.

Background/aims: We aimed to explore the effects of hepatitis C virus (HCV) core and NS5A proteins on reactive oxygen (ROS) and nitrogen species (RNS) formation and on gene expression profile of iNOS in human hepatocyte-derived cells., Methods: Production of ROS and RNS and nitrotyrosine residues accumulation were determined by flow cytometry and fluorescent microscopy as well as by Western blot, respectively, in NS5A- and core-transfected cells. Northern blot, Western blot, real-time PCR, and luciferase assays were used to assess iNOS gene expression in both transfectants., Results: Cytokine-activated NS5A- and core-transfected cells induced ROS and RNS production but an earlier and more marked increase was observed in NS5A-expressing cells. Superoxide production was also augmented, showing a similar temporal pattern of appearance in both NS5A- and core-transfected cells. Although both NS5A and core HCV proteins were able to up-regulate iNOS gene expression, accompanied by a nitrotyrosine-containing proteins accumulation, an earlier iNOS overexpression was observed in NS5A-expressing cells, suggesting a different time course of iNOS activation pattern for core and NS5A HCV proteins., Conclusions: Our results indicate a differential contribution of both HCV proteins to oxidative and nitrosative stress generation.