Instruments for the Identification of Child Sexual Exploitation: A Systematic Review.

To perform a systematic search of instruments for the early identification of risk of sexual exploitation in children (CSE) and appraise their metric properties. Searches were conducted in four electronic databases to identify instruments that only evaluated child sexual exploitation with no restrictions of date or language. Two reviewers independently carried out the initial selection of titles and abstracts, appraisal of the methodological quality, compliance with the entry criteria in the analysis, and extraction of data necessary to systematize the information available. Twenty-three articles were found that used 15 CSE detection instruments. The instruments varied with regard to number of questions, ease of administration, sources of information, rating methods, and the training information provided. What they had in common is that most were designed and used in the English-speaking world, basically in the United States, with few instruments providing solid proof of their validity and reliability in the scores derived thereof. Although instruments were obtained with significant similarities in their conceptualization, differences in multiple characteristics made it difficult to draw clear conclusions regarding their greater or lesser suitability. What did become clear was the need to keep working on obtaining rigorous empirical psychometric evidence.

SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replication.

Serine incorporator protein 5 (SERINC5) is a key innate immunity factor that operates in the cell to restrict the infectivity of certain viruses. Different viruses have developed strategies to antagonize SERINC5 function but, how SERINC5 is controlled during viral infection is poorly understood. Here, we report that SERINC5 levels are reduced in COVID-19 patients during the infection by SARS-CoV-2 and, since no viral protein capable of repressing the expression of SERINC5 has been identified, we hypothesized that SARS-CoV-2 non-coding small viral RNAs (svRNAs) could be responsible for this repression. Two newly identified svRNAs with predicted binding sites in the 3'-untranslated region (3'-UTR) of the SERINC5 gene were characterized and we found that the expression of both svRNAs during the infection was not dependent on the miRNA pathway proteins Dicer and Argonaute-2. By using svRNAs mimic oligonucleotides, we demonstrated that both viral svRNAs can bind the 3'UTR of SERINC5 mRNA, reducing SERINC5 expression in vitro. Moreover, we found that an anti-svRNA treatment to Vero E6 cells before SARS-CoV-2 infection recovered the levels of SERINC5 and reduced the levels of N and S viral proteins. Finally, we showed that SERINC5 positively controls the levels of Mitochondrial Antiviral Signalling (MAVS) protein in Vero E6. These results highlight the therapeutic potential of targeting svRNAs based on their action on key proteins of the innate immune response during SARS-CoV-2 viral infection.

New roles for AP-1/JUNB in cell cycle control and tumorigenic cell invasion via regulation of cyclin E1 and TGF-ß2.

BACKGROUND: JUNB transcription factor contributes to the formation of the ubiquitous transcriptional complex AP-1 involved in the control of many physiological and disease-associated functions. The roles of JUNB in the control of cell division and tumorigenic processes are acknowledged but still unclear. RESULTS: Here, we report the results of combined transcriptomic, genomic, and functional studies showing that JUNB promotes cell cycle progression via induction of cyclin E1 and repression of transforming growth factor (TGF)-ß2 genes. We also show that high levels of JUNB switch the response of TGF-ß2 stimulation from an antiproliferative to a pro-invasive one, induce endogenous TGF-ß2 production by promoting TGF-ß2 mRNA translation, and enhance tumor growth and metastasis in mice. Moreover, tumor genomic data indicate that JUNB amplification associates with poor prognosis in breast and ovarian cancer patients. CONCLUSIONS: Our results reveal novel functions for JUNB in cell proliferation and tumor aggressiveness through regulation of cyclin E1 and TGF-ß2 expression, which might be exploited for cancer prognosis and therapy.

Detección de la explotación sexual en la infancia y la adolescenciamediante la evaluación de indicadores de riesgo en España / Detection of Child Sexual Exploitation Through the Evaluation of Risk Indica- tors in Spain

La explotación sexual infantil y adolescente en España es un problema que requiere de una detección temprana de susvíctimas. Son escasas las herramientas que permitan llevar a cabo esta detección y no se dispone de ninguna en lenguaespañola. En este estudio se presenta una herramienta para la valoración del riesgo de sufrir explotación sexual enmenores desde los 11 años mediante la selección de aquellos indicadores que mejor la predicen. A partir de una revisiónsistemática de publicaciones en Europa, se preparó una batería de indicadores, los cuales fueron estudiados y filtradosen una consulta a expertos mediante panel Delphi para generar el primer instrumento que fue sometido a valoración enuna segunda fase de consulta con profesionales considerados como pares. El diseño final se acabó de perfilar por cuatroexpertos de universidades españolas. La herramienta de detección del riesgo de explotación sexual en la infancia yadolescencia EDR-ESIA ha demostrado ser un buen instrumento de detección y cribado, para su aplicación en servicioseducativos, de atención primaria de salud y servicios sociales de nuestro país.(AU)

Child sexual exploitation in Spain is a problem that requires the early detection of victims. There are few tools thatenable this detection, and none are available in Spanish. This study presents a tool for assessing the risk of sufferingsexual exploitation in minors from 11 years of age, by selecting the indicators that best predict it. Based on a systematicreview of publications in Europe, a battery of indicators was prepared, then studied and filtered via consultation withexperts using a Delphi panel to create the first instrument, which was then evaluated in a second phase consultationwith professionals considered as peers. The final construct was completed by four experts from Spanish universities.The tool for detecting the risk of sexual exploitation in childhood and adolescence, EDR-ESIA, has proven to be a gooddetection and screening instrument, for application in educational services, primary health care, and social services.(AU)

Commercial Sexual Exploitation of Children and Adolescents in Europe: A Systematic Review.

OBJECTIVES: The objective of this review is to provide a systematic and critical summary of findings regarding empirical studies conducted on commercial sexual exploitation of children (CSEC) in Europe. The purpose is to gain an understanding of the characteristics and main topics addressed in European research on CSEC, identify gaps, and give suggestions for future studies. METHOD: The review was guided by the "Preferred Reporting Items for Systematic Review and Meta-Analysis-Protocols". A comprehensive search on several databases was conducted to identify published and unpublished empirical research on CSEC in Europe, revealing 3,846 documents. In total, 56 research papers that focused specifically on CSEC in European samples were included. SYNTHESIS: Research concerning European studies of CSEC and trafficking for purposes of sexual exploitation has developed significantly over the last 20 years but is still rather limited and mainly focused on the UK and Sweden. Most of the studies reviewed suffer from important methodological flaws such as an inaccurate definition of the phenomenon analyzed, small and convenience samples, and nonvalidated and nonspecific instruments. CONCLUSIONS: Findings from this study demonstrate the need for greater exploration and research around a number of areas of sexual exploitation of children in Europe. Further work is necessary in terms of capacity building, training, and awareness-raising for society as a whole and, specifically, professionals providing direct support to children and young people at risk of exploitation.

Risk Factors for Commercial Sexual Exploitation of Children and Adolescents: Results of an International Delphi Panel.

BACKGROUND: Commercial sexual exploitation of children and adolescents (CSECA) is a worldwide problem. The need to improve current detection and intervention protocols motivated this analysis, which aimed to use expert opinion to identify indicators (symptoms, conduct, or behaviors) that may help to predict the risk of suffering CSECA and to detect those who are suffering from it, as well as the type of detection tools and protocols that should be used. METHOD: An international multidisciplinary group of experts in CSECA was invited to take part in this study. A two-round digital Delphi panel was undertaken with 22 experts. An ad hoc questionnaire was created, which included 41 questions about CSECA risk factors and interventions that should be considered during detection. RESULTS: The main indicators identified included normalization of dynamics of sexual exchange within the family, family history of sexual exploitation, and sexually transmitted infections. Predictive characteristics included economic extortion, lack of documentation, and family estrangement. Additionally, 95.5% of participants agreed that multiple victimizations in childhood should be considered for CSECA detection. CONCLUSIONS: This study provides information that may be very useful in the development/improvement of instruments for CSECA detection. With this approach we hope to promote the creation of tools adapted to the Spanish cultural context.

Ubiquitin-Regulated Cell Proliferation and Cancer.

Ubiquitin ligases (E3) play a crucial role in the regulation of different cellular processes such as proliferation and differentiation via recognition, interaction, and ubiquitination of key cellular proteins in a spatial and temporal regulated manner. The type of ubiquitin chain formed determines the fate of the substrates. The ubiquitinated substrates can be degraded by the proteasome, display altered subcellular localization, or can suffer modifications on their interaction with functional protein complexes. Deregulation of E3 activities is frequently found in various human pathologies, including cancer. The illegitimated or accelerated degradation of oncosuppressive proteins or, inversely, the abnormally high accumulation of oncoproteins, contributes to cell proliferation and transformation. Anomalies in protein abundance may be related to mutations that alter the direct or indirect recognition of proteins by the E3 enzymes or alterations in the level of expression or activity of ubiquitin ligases. Through a few examples, we illustrate here the complexity and diversity of the molecular mechanisms related to protein ubiquitination involved in cell cycle regulation. We will discuss the role of ubiquitin-dependent degradation mediated by the proteasome, the role of non-proteolytic ubiquitination during cell cycle progression, and the consequences of this deregulation on cellular transformation. Finally, we will highlight the novel opportunities that arise from these studies for therapeutic intervention.

Polyamines interfere with protein ubiquitylation and cause depletion of intracellular amino acids: a possible mechanism for cell growth inhibition.

Spermidine is a polyamine present in eukaryotes with essential functions in protein synthesis. At high concentrations spermidine and norspermidine inhibit growth by unknown mechanisms. Transcriptomic analysis of the effect of norspermidine on the plant Arabidopsis thaliana indicates upregulation of the response to heat stress and denatured proteins. Accordingly, these polyamines inhibit protein ubiquitylation, both in vivo (in yeast, Arabidopsis, and human Hela cells) and in vitro (with recombinant ubiquitin ligase). This interferes with protein degradation by the proteasome, a situation known to deplete cells of amino acids. Norspermidine treatment of yeast cells induces amino acid depletion, and supplementation of media with amino acids counteracts growth inhibition and cellular amino acid depletion but not inhibition of protein polyubiquitylation.

Cell Synchronization Techniques to Study the Action of CDK Inhibitors.

Cell synchronization techniques have been used for the studies of mechanisms involved in cell cycle regulation. Synchronization involves the enrichment of subpopulations of cells in specific stages of the cell cycle. These subpopulations are then used to study regulatory mechanisms of the cell cycle such as DNA synthesis, gene expression, protein synthesis, protein phosphorylation, protein degradation, and development of new drugs (e.g., CDK inhibitors). Here, we describe several protocols for synchronization of cells from different phases of the cell cycle. We also describe protocols for determining cell viability and mitotic index and for validating the synchrony of the cells by flow cytometry.