In vivo testing of gold nanoparticles using the Caenorhabditis elegans model organism

Gold nanoparticles (AuNPs) are present in many man-made products and cosmetics, and are also used by the food and medical industries. Tight regulations regarding the use of mammalian animals for product testing can hamper the study of the specific interactions between engineered nanoparticles and biological systems. Invertebrate models, such as the nematode Caenorhabditis elegans (C. elegans), can offer alternative approaches during the early phases of nanoparticle discovery. Here, we thoroughly evaluated the biodistribution of 11-nm and 150-nm citrate-capped AuNPs in the model organism C. elegans at multiple scales, moving from micrometric to nanometric resolution and from the organismal to cellular level. We confirmed that the nanoparticles were not able to cross the intestinal and dermal barriers. We investigated the effect of AuNPs on the survival and reproductive performance of C. elegans, and correlated these effects with the uptake of AuNPs in terms of their number, surface area, and metal mass. In general, exposure to 11-nm AuNPs resulted in a higher toxicity than the larger 150-nm AuNPs. NP aggregation inside C. elegans was determined using absorbance microspectroscopy, which allowed the plasmonic properties of AuNPs to be correlated with their confinement inside the intestinal lumen, where anatomical traits, acidic pH and the presence of biomolecules play an essential role on NP aggregation. Finally, quantitative PCR of selected molecular markers indicated that exposure to AuNPs did not significantly affect endocytosis and intestinal barrier integrity. Statement of significance This work highlights how the simple, yet information-rich, animal model C. elegans is ideally suited for preliminary screening of nanoparticles or chemicals mitigating most of the difficulties associated with mammalian animal models, namely the ethical issues, the high cost, and time constraints. This is of particular relevance to the cosmetic, food, and pharmaceutical industries, which all have to justify the use of animals, especially during the discovery, development and initial screening phases. This work provides a detailed and thorough analysis of 11-nm and 150-nm AuNPs at multiple levels of organization (the whole organism, organs, tissues, cells and molecules).Peer ReviewedPostprint (author's final draft

Gestational Thrombophilia: Main Approaches to Diagnosis and Treatment

The woman\u27s body undergoes several physiological changes during the gestational period. Risk factors and comorbidities can cause pathophysiological changes in this period, especially in the maternal vascular system, triggering thrombophilia. This clotting disorder increases the thrombus formation risk, especially in the uteroplacental circulation. The study aimed to conduct a thorough review of the main approaches to diagnosis and treatment in reducing patient morbidity and mortality. This is an integrative review with qualitative data searched in Pubmed, BVS and Cochrane Library. A total of 624 studies were found, 591 were excluded outside the inclusion criteria, and 33 were selected. According to the careful search, thrombophilias can be hereditary or acquired, the former when there is a predisposition to venous occlusion and the latter from other clinical conditions. Pregnancy is a pro-thrombotic event and increases the chances of thrombus occurrence, triggering a series of pregnancy complications, such as intrauterine death, early or late miscarriage, and premature birth. However, if diagnosed early, there is a favorable prognosis for the woman and the fetus. To reduce these impacts of gestational thrombophilia, it is imperative to train primary health care and private clinics professionals to promote and treat health and basic diagnostic tests on pregnant women. Thus, performing early intervention avoiding the development of maternal-fetal complications

Análise global da expressão gênica diferencial no Câncer de mama Triplo Negativo Global

O câncer de mama está entre as neoplasias que mais afetam mulheres no Brasil. Dentre os subtipos, destaca-se o Câncer de Mama Triplo Negativo (TNBC) com a maior malignidade, caracterizado pela ausência dos receptores de estrógeno, progesterona e do fator de crescimento epidérmico. Esse trabalho buscou elucidar, por meio de ferramentas computacionais e análises de dados genéticos, os principais genes diferencialmente expressos encontrados exclusivamente no subtipo TNBC, comparando-o com os demais e com tecidos de mama normais. Para isso, foi utilizada a plataforma de análise UALCAN, e GEPIA para validação das expressões genéticas. Dos 250 genes up-regulados, foram encontrados 92 exclusivos de TNBC, e dos 250 genes down-regulados, 53. Dentre esses, foram caracterizados como potenciais alvos terapêuticos e marcadores de prognóstico os genes IQGAP3, HJURP, FAM64a, TAT e HMGCS2, porém são necessários estudos mais aprofundados sobre as funções biológicas de cada um

In vivo testing of gold nanoparticles using the Caenorhabditis elegans model organism

Gold nanoparticles (AuNPs) are present in many man-made products and cosmetics, and are also used by the food and medical industries. Tight regulations regarding the use of mammalian animals for product testing can hamper the study of the specific interactions between engineered nanoparticles and biological systems. Invertebrate models, such as the nematode Caenorhabditis elegans (C. elegans), can offer alternative approaches during the early phases of nanoparticle discovery. Here, we thoroughly evaluated the biodistribution of 11-nm and 150-nm citrate-capped AuNPs in the model organism C. elegans at multiple scales, moving from micrometric to nanometric resolution and from the organismal to cellular level. We confirmed that the nanoparticles were not able to cross the intestinal and dermal barriers. We investigated the effect of AuNPs on the survival and reproductive performance of C. elegans, and correlated these effects with the uptake of AuNPs in terms of their number, surface area, and metal mass. In general, exposure to 11-nm AuNPs resulted in a higher toxicity than the larger 150-nm AuNPs. NP aggregation inside C. elegans was determined using absorbance microspectroscopy, which allowed the plasmonic properties of AuNPs to be correlated with their confinement inside the intestinal lumen, where anatomical traits, acidic pH and the presence of biomolecules play an essential role on NP aggregation. Finally, quantitative PCR of selected molecular markers indicated that exposure to AuNPs did not significantly affect endocytosis and intestinal barrier integrity. Statement of significance This work highlights how the simple, yet information-rich, animal model C. elegans is ideally suited for preliminary screening of nanoparticles or chemicals mitigating most of the difficulties associated with mammalian animal models, namely the ethical issues, the high cost, and time constraints. This is of particular relevance to the cosmetic, food, and pharmaceutical industries, which all have to justify the use of animals, especially during the discovery, development and initial screening phases. This work provides a detailed and thorough analysis of 11-nm and 150-nm AuNPs at multiple levels of organization (the whole organism, organs, tissues, cells and molecules).Peer Reviewe

Psychodrama in therapeutic communities for drug addiction: A study of four cases investigated using idiographic change process analysis

Many psychotherapeutic models, including psychodrama, have tried to address the problem of drugaddiction and alcoholism within, and outside, therapeutic communities (TCs). The dearth of literature related to the application of psychodrama in TCs means that significant efforts are needed to show its effectiveness. This article derives from a TC in northern Italy and presents a study of four cases, which analyzed the results of a 6 month psychodrama research intervention that adopted the Person Centered Approach (PCA). The effects were measured through an idiographic change process with a mixed method design. The qualitative part of the assessment consisted of the Client Change Interview (CCI), the Helpful Aspects of Therapy (HAT); the longitudinal quantitative part used the Spontaneity Assessment Inventory 12 Revised (SAI-R), the Clinical Outcomes in Routine Evaluation 12 Outcome Measure (CORE-OM), the General Self-Efficacy Scale (GS-ES), and the Pro.Spera. The changes in main personality factors were evaluated through Minnesota Multiphasic Personality Inventory (MMPI). Results suggested on the one hand that psychodrama therapy may increase patients\u2019 self-awareness and motivation to change their way of life and improve the PCA. On the other hand the qualitative methodology of HAT and CCI demonstrated, and monitored, the process of change and empowerment in the patients. Finally, the subject of gender specificity is explored