148 research outputs found

    Psychosocial and behavioral impact of COVID-19 in autism spectrum disorder: an online parent survey

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    The 2019 coronavirus disease (COVID-19) outbreak could result in higher levels of psychological distress, especially among people suffering from pre-existing mental health conditions. Young individuals with autism spectrum disorders (ASD) are particularly at risk due to their vulnerability to unpredictable and complex changes. This study aimed to investigate the impact of the COVID-19 pandemic on ASD individuals, whether any pre-pandemic sociodemographic or clinical characteristics would predict a negative outcome, and to narratively characterize their needs. Parents and guardians of ASD individuals filled out an online survey consisting of 40 questions investigating socio-demographic and clinical characteristics of their children, impact of the COVID-19 outbreak on their wellbeing and needs to deal with the emergency. Data were available on 527 survey participants. The COVID-19 emergency resulted in a challenging period for 93.9% of families, increased difficulties in managing daily activities, especially free time (78.1%) and structured activities (75.7%), and, respectively, 35.5% and 41.5% of children presenting with more intense and more frequent behavior problems. Behavior problems predating the COVID-19 outbreak predicted a higher risk of more intense (odds ratio (OR) = 2.16, 95% confidence interval (CI) 1.42-3.29) and more frequent (OR = 1.67, 95% CI 1.13-2.48) disruptive behavior. Even though ASD children were receiving different types of support, also requiring specialist (19.1%) or emergency (1.5%) interventions in a relatively low proportion of cases, a number of needs emerged, including receiving more healthcare support (47.4%), especially in-home support (29.9%), as well as interventions to tackle a potentially disruptive quarantine (16.8%). The COVID-19 outbreak has undoubtedly resulted in increased difficulties among ASD individuals

    The Possible Role of Prescribing Medications, Including Central Nervous System Drugs, in Contributing to Male-Factor Infertility (MFI): Assessment of the Food and Drug Administration (FDA) Pharmacovigilance Database

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    © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Background: A wide range of medications may have a possible role in the development of male-factor infertility (MFI), including various antineoplastic agents, testosterone/anabolic steroids, immunosuppressive drugs/immunomodulators, glucocorticosteroids, non-steroidal an-ti-inflammatory drugs, opiates, antiandrogenic drugs/5-alpha-reductase inhibitors, various antibi-otics, antidepressants, antipsychotics, antiepileptic agents and others. We aimed at investigating this issue from a pharmacovigilance-based perspective. Methods: The Food and Drug Administra-tion (FDA) Adverse Event Reporting System (FAERS) database was queried to identify the drugs associated the most with MFI individual reports. Only those drugs being associated with more than 10 MFI reports were considered for the disproportionality analysis. Proportional Reporting Ratios (PRRs) and their confidence intervals were computed for all the drugs identified in this way in January 2023. Secondary, ‘unmasking’, dataset analyses were carried out as well. Results: Out of the whole database, 955 MFI reports were identified, 408 (42.7%) of which were associated with 20 medications ,which had more than 10 reports each. Within this group, finasteride, testosterone, valproate, diethylstilbestrol, mechloretamine, verapamil, lovastatin and nifedipine showed signif-icant levels of actual disproportionate reporting. Out of these, and before unmasking, the highest PRR values were identified for finasteride, diethylstilbestrol and mechloretamine, respectively, with values of 16.0 (12.7–20.3), 14.3 (9.1–22.4) and 58.7 (36.3–95.9). Conclusions: A variety of several medications, a number of which were already supposed to be potentially linked with MFI based on the existing evidence, were associated with significant PRR levels for MFI in this analysis. A number of agents which were previously hypothesized to be associated with MFI were not represented in this analysis, suggesting that drug-induced MFI is likely under-reported to regulatory agencies. Reproductive medicine specialists should put more effort into the detection and reporting of these adverse drug reactions.Peer reviewe

    Using Glycerol to Produce European Sea Bass Feed With Oleaginous Microbial Biomass: Effects on Growth Performance, Filet Fatty Acid Profile, and FADS2 Gene Expression

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    Using a circular economy concept, the present study investigated the use of crude glycerol, a primary by-product of biodiesel production, as a low-priced nutrient source for heterotrophic cultivation of the fungus-like protist Schizochytrium limacinum SR21 strain. The whole biomass of this oleaginous microorganism, rich in docosahexaenoic acid (DHA) and high-quality proteins, was then paired with a vegetable oil (VO) source and used to replace fish oil (FO) in European sea bass (Dicentrarchus labrax) feeds. Four nutritionally balanced diets were formulated: diet FO (a FO-based diet), diet VO + 0 (a VO-based diet without S. limacinum), and diets VO + 5 and VO + 10 that were VO-based feeds supplemented with 5 and 10% of S. limacinum, respectively. After a 3-month feeding trial, fish of all dietary groups tripled their initial weight, but growth and feeding efficiencies of D. labrax were not significantly different among treatments. Although the formulated diets were balanced for polyunsaturated fatty acids (PUFAs), fish fed with feeds containing either VO or VO plus 5 and 10% of S. limacinum biomass had significantly higher levels of PUFAs in the flesh than fish fed the FO-based diet. Values of health-related lipid indexes, such as atherogenicity index, thrombogenicity index, and flesh lipid quality as well as n-6/n-3 and PUFAs/SFAs ratios confirmed the high nutritional value of sea bass filet, thus representing a healthy product for human consumption. Although the PUFAs/SFAs ratio showed a significantly higher value in fish fed with VO-based diets supplemented with S. limacinum than in those fed with FO diet, suggesting a better filet quality, the n-6/n-3 ratio clearly indicated that filet quality of dietary group FO was best (value of 0.55) and that of group VO + 10 second best (value of 0.98). We also evaluated the nutritional regulation of 16-desaturase (or fads2) gene expression in European sea bass liver. European sea bass fed the VO + 0 diet had the highest number of mRNA copies for 16-desaturase (or fads2), fish fed with diet VO + 10 the lowest. Our study adds to the growing body of literature concerning the use of thraustochytrid biomass as a valid alternative to marine-derived raw materials for European sea bass feeds

    Alternativas para la reducción del volumen y masa de residuos sólidos urbanos destinados a enterramiento en la ciudad de Unquillo mediante la implementación de tratamiento mecánico biológico (TMB)

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    Luego de 20 años de mejoras graduales en la gestión de residuos, comenzando por el cierre del basural en 2002, el Municipio de Unquillo (18.000 habitantes, Provincia de Córdoba) se encuentra con desafíos como disminuir la cantidad de residuos a transferir al relleno sanitario de la ciudad de Córdoba, distante a 55 km. Para reducir los costos de transporte y disposición final de los residuos no captados por la recolección diferenciada, se están implementando medidas para disminuirla generación y aumentar el reciclaje. Aun así, la fracción húmeda contiene una importante cantidad de materiales reciclables. En el presente trabajo se desarrolla una prueba piloto de tratamiento mecánico biológico (TMB) de esta fracción de residuos sólidos urbanos (RSU). El TMB combina la clasificación y procesamiento mecánico con el tratamiento biológico, con el objetivo de reducir la masa y volumen y estabilizar los RSU. Se realizaron dos pruebas de TMB, en verano y en invierno, que procesaron más de dos toneladas de RSU. El presenta trabajo tiene como objetivo valorar el potencial que (TMB) tiene como alternativa tecnológica de tratamiento de los RSU antes de derivarlos a disposición final. Los resultados muestran que es posible recuperar un 27% en peso de materiales reciclables y derivar a compostaje un 44% con lo que sólo se debería enviar a disposición menos de 30% de la masa recibida. Además, se estimó que el rendimiento de cada operario en la separación es de unos 70 kg/hora.En términos económicos, el costo del personal adicional 1.117 mil pesos al año, se compensa por los ahorros deFil: Antonini, Sebastian. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Ingeniería Química; Argentina.Fil: Pettigiani, Eugenio. Instituto Nacional de Tecnología Industrial. Unidad de Extensión Córdoba; Argentina.Fil: Silva, Federico. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Ingeniería Química. Estudiante; Argentina.Fil: Cravero, Leandro. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Ingeniería Química. Estudiante; Argentina.Fil: Reynafé, Lautaro. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Ingeniería Química. Estudiante; Argentina.Fil: Cuffia, Carolina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Ingeniería Química. Estudiante; Argentina.Ingeniería de Procesos Químico

    USP14 inhibition corrects an in vivo model of impaired mitophagy

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    Mitochondrial autophagy or mitophagy is a key process that allows selective sequestration and degradation of dysfunctional mitochondria to prevent excessive reactive oxygen species, and activation of cell death. Recent studies revealed that ubiquitin-proteasome complex activity and mitochondrial membrane rupture are key steps preceding mitophagy, in combination with the ubiquitination of specific outer mitochondrial membrane (OMM) proteins. The deubiquitinating enzyme ubiquitin-specific peptidase 14 (USP14) has been shown to modulate both proteasome activity and autophagy. Here, we report that genetic and pharmacological inhibition of USP14 promotes mitophagy, which occurs in the absence of the well-characterised mediators of mitophagy, PINK1 and Parkin. Critical to USP14-induced mitophagy is the exposure of the LC3 receptor Prohibitin 2 by mitochondrial fragmentation and mitochondrial membrane rupture. Genetic or pharmacological inhibition of USP14 in vivo corrected mitochondrial dysfunction and locomotion behaviour of PINK1/Parkin mutant Drosophila model of Parkinson's disease, an age-related progressive neurodegenerative disorder that is correlated with diminished mitochondrial quality control. Our study identifies a novel therapeutic target that ameliorates mitochondrial dysfunction and in vivo PD-related symptoms

    YAP contributes to DNA methylation remodeling upon mouse embryonic stem cell differentiation

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    The Yes-associated protein YAP, one of the major effectors of the Hippo pathway together with its related protein TAZ, mediates a range of cellular processes from proliferation and death to morphogenesis. YAP and TAZ regulate a large number of target genes, acting as co-activators of DNA-binding transcription factors or as negative regulators of transcription by interacting with the nucleosome remodeling and histone deacetylase complexes. YAP is expressed in self-renewing embryonic stem cells (ESCs), although it is still debated whether it plays any crucial roles in the control of either stemness or differentiation. Here we show that the transient downregulation of YAP in mouse ESCs perturbs cellular homeostasis, leading to the inability to differentiate properly. Bisulfite genomic sequencing revealed that this transient knockdown caused a genome-wide alteration of the DNA methylation remodeling that takes place during the early steps of differentiation, suggesting that the phenotype we observed might be due to the dysregulation of some of the mechanisms involved in regulation of ESC exit from pluripotency. By gene expression analysis we identified two molecules which could have a role in the altered genome-wide methylation profile: the long non-coding RNA Ephemeron, whose rapid upregulation is crucial for ESCs transition into epiblast, and the methyltransferase-like protein Dnmt3l, which, during the embryo development, cooperates with Dnmt3a and Dnmt3b to contribute to the de novo DNA methylation that governs early steps of ESC differentiation. These data suggest a new role for YAP in the governance of the epigenetic dynamics of exit from pluripotency

    Quantum dots labelling allows detection of the homing of mesenchymal stem cells administered as immunomodulatory therapy in an experimental model of pancreatic islets transplantation

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    Cell transplantation is considered a promising therapeutic approach in several pathologies but still needs innovative and non-invasive imaging technologies to be validated. The use of mesenchymal stem cells (MSCs) attracts major interest in clinical transplantation thanks to their regenerative properties, low immunogenicity and ability to regulate immune responses. In several animal models, MSCs are used in co-transplantation with pancreatic islets (PIs) for the treatment of type I diabetes, supporting graft survival and prolonging normal glycaemia levels. In this study we investigated the homing of systemically administered MSCs in a rat model of pancreatic portal vein transplantation. MSCs labelled with quantum dots (Qdots) were systemically injected by tail vein and monitored by optical fluorescence imaging. The fluorescence signal of the liver in animals co-transplanted with MSCs and PIs was significantly higher than in control animals in which MSCs alone were transplanted. By using magnetic labelling of PIs, the homing of PIs into liver was independently confirmed. These results demonstrate that MSCs injected in peripheral blood vessels preferentially accumulate into liver when PIs are transplanted in the same organ. Moreover, we prove that bimodal MRI-fluorescence imaging allows specific monitoring of the fate of two types of cells
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