Measuring Cyber Dating Violence: Reliability and Validity of the Escala de CiberViolencia en Parejas Adolescentes (Cib-VPA) in Spanish Young Adults / La evaluación de la ciberviolencia en el noviazgo: fiabilidad y validez de la Escala de Ciber-Violencia en Parejas Adolescentes (Cib-VPA) en adultos jóvenes españoles

The aim of this study was to obtain validity evidence of the Escala de Ciber-Violencia en Parejas Adolescentes (Cib-VPA) in the Spanish young adults. A total of 298 undergraduate students (222 women, 75 men and 2 people who identified themselves as ‘other’) completed the Cib-VPA and other related measures of offline and online dating violence. Internal consistency and construct, convergent and discriminant validity were evaluated. In line with the original validation study, a confirmatory factor analysis (CFA) provided evidence for an 18-item model comprising 2 subscales, with 2 factors per subscale. All had acceptable internal consistency values. Total and subscale scores correlated positively with online and offline dating violence measures, with these correlations being stronger in subscales evaluating violence in the same direction (perpetrated or victimisation). As expected, no differences were observed according to gender. This study shows validity evidences of Cib-VPA scores, which can be quickly and inexpensively administered to large samples of young adults. (AU)

El objetivo de este estudio fue poner a prueba la validez de la Escala de Ciber-Violencia en Parejas Adolescentes (Cib-VPA) en adultos jóvenes españoles. Un total de 298 estudiantes universitarios (222 mujeres, 75 hombres y 2 personas que se identificaron como “otros”) cumplimentaron la Cib-VPA y otras medidas relacionadas con la violencia en el noviazgo, convencional y ciberviolencia. Se evaluó la consistencia interna y la validez de constructo, convergente y discriminante. En consonancia con el estudio de validación original, un análisis factorial confirmatorio (AFC) evidenció un modelo de 18 ítems compuesto por 2 subescalas, con 2 factores por subescala. Todos tenían valores de consistencia interna aceptables. Las puntuaciones totales y de las subescalas correlacionaron positivamente con las medidas de violencia en el noviazgo, tanto convencional como ciberviolencia, siendo estas correlaciones más fuertes en las subescalas que evalúan la violencia en la misma dirección (perpetrada o victimización). Como se esperaba, no se observaron diferencias en función del género. Este estudio confirma la validez de las puntuaciones del Cib-VPA, que puede ser administrado de forma rápida y económica a grandes muestras de jóvenes adultos. (AU)

Design and Validation of a Scale for Measuring Well-Being of Children in Lockdown (WCL).

The objective of this study was to create and validate an instrument to measure the well-being of children in lockdown. As a response to the COVID-19 pandemic, and in the interest of maintaining social distancing, millions of people have been confined to their homes, including children, who have been withdrawn from school and barely able to leave their homes. Thus, it would be useful to evaluate, from a holistic perspective, the well-being of children under these challenging circumstances. The participants were 1,046 children, 48.7% of which were boys and 50.7% girls, recruited in the Basque Country (Northern Spain). The scale was answered by their parents. The survey, entitled "Well-being of Children in Lockdown" (WCL), is composed of six subscales: Emotions, Playful and creative activities, Education, Addictions, Routine, and Physical Activity. Exploratory factor analyses indicate that all the reliability indices were acceptable. The survey demonstrated adequate reliability (alpha = 0.804). We were thus able to confirm the validity of this simple instrument for evaluating the well-being of children aged between 4 and 12 years in lockdown situations. The WCL can be regarded as a useful tool to evaluate the well-being of children in lockdown situations.

Teen Dating Violence, Sexism, and Resilience: A Multivariate Analysis.

The aim of this research was to know the factors associated with teen dating violence and victimization because violence in teenagers' relationships is increasing in recent years, constituting a serious social problem. For this purpose, we analyzed teen dating violence and explored the variables (sexist attitudes, personal adjustment, clinical maladjustment, and resilience) related to teen dating violence and victimization using multinomial logistic models. The sample was composed of 268 school teenagers aged 12 to 17 from the Basque Country (Spain). Results showed that sex, age, sexism, and self-esteem predicted teen dating violence and that sex and social problems predicted victimization. Associations between the wide range of variables and types of perpetration and victimization (verbal-emotional, relational, and physical) were also explored. These results could be taken into consideration for future prevention programs.

Psychological Symptoms in Health Professionals in Spain After the First Wave of the COVID-19 Pandemic.

Following the declaration of the COVID-19 outbreak as a global pandemic in March 2020, a state of alarm was decreed in Spain. In this situation, healthcare workers experienced high levels of stress, anxiety and depression due to the heavy workload and working conditions. Although Spain experienced a progressive decline in the number of COVID-19 cases until the last week of May (when a flattening of the case curve was achieved) and the work overload among health workers was substantially reduced, several studies have shown that this work overload is associated with the later emergence of psychological symptoms induced by stress. The aim of the present study was to evaluate the levels of stress, anxiety, depression, post-traumatic stress and compassionate fatigue in health professionals. The sample consisted of 973 health professionals 16.5% men, 82.9% women, and one non-binary person. The data were collected through an online questionnaire sent to the participants by e-mail. DASS-21 was used to measure anxiety, stress and depression, PCL-C to measure post-traumatic stress and ProQOL -vIV to measure compassion fatigue. In addition, other descriptive variables that could be related to these levels of psychological symptomatology were evaluated. The results reveal that after the work overload experienced during the COVID-19 pandemic, healthcare workers report psychological symptoms, post-traumatic stress and compassion fatigue. It is therefore recommended that these professionals be provided with psychological help in order to reduce the emotional impact of COVID-19, and consequently improve their mental health.

Variables Related to Victimization and Perpetration of Dating Violence in Adolescents in Residential Care Settings.

Violence in dating relationships constitutes a serious problem, thus, the study of related factors could help to better understand this violence and intervene in it. This study had three goals: (1) To analyze the prevalence of dating violence in adolescents under residential care settings according to sex and age; (2) to explore the relationships between victimization and perpetration in adolescents' dating violence, sexist attitudes and clinical variables; and (3) to identify variables associated to adolescents' dating violence (victimization and perpetration). The sample comprised 271 adolescents (54.6% boys and 45.4% girls), aged between 12 and 17 years (M = 15.23, SD = 1.60). The victimization (R2 = .17, p <.001) and perpetration (R2 = .20. p < .001) results showed prevalence rates higher than those of previous studies. Sex was not a differentiating factor for perpetration of dating violence, but age was: the older they were, the higher the perpetration rate. In the case of victimization, an interaction between sex and age was found. Results showed that age, sex, hostile sexism and depression were variables associated to victimization whereas age, hostile sexism and depression were associated to perpetration of dating violence.

Tumor suppressive function of E2F-1 on PTEN-induced serrated colorectal carcinogenesis.

Many human cancers present Phosphatase and tensin homolog (PTEN) deficiency and between 20 and 30% of colorectal tumors show PTEN loss. The transcription factor, E2 promoter binding factor 1 (E2F-1), exhibits tumor promoter or suppressive functions depending on cellular type and tissue context, but its role in the progression and development of colorectal carcinogenesis was largely unknown. Here, using a tamoxifen-inducible PTEN knockout mouse model, we have demonstrated that loss of PTEN leads to the development of colorectal tumorigenesis through the serrated pathway. Next, we studied PTEN loss-driven colorectal lesions in the context of E2F-1 deficiency in vivo. Our results revealed that monoallelic and biallelic absence of E2F-1 led to an increased incidence and progression of serrated tumorigenesis induced by PTEN loss. Finally, we investigated the mechanisms by which double PTEN/E2F-1 deficiency leads to enhanced tumorigenesis. We found that colorectal tumors from PTEN/E2F-1 double knockout mice and the human colorectal carcinoma cell line HT29 with shRNA-mediated downregulation of PTEN and E2F-1 exhibit hyperactivation of the RAS-MAPK pathway, accumulation of DNA damage and resistance to apoptosis. To date, this is the first preclinical study evaluating the effect of genetic deletion of E2F-1 in colorectal malignancies driven by PTEN deficiency. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Variables related to victimization and perpetration of dating violence in adolescents in residential care settings

Violence in dating relationships constitutes a serious problem, thus, the study of related factors could help to better understand this violence and intervene in it. This study had three goals: (1) To analyze the prevalence of dating violence in adolescents under residential care settings according to sex and age; (2) to explore the relationships between victimization and perpetration in adolescents' dating violence, sexist attitudes and clinical variables; and (3) to identify variables associated to adolescents' dating violence (victimization and perpetration). The sample comprised 271 adolescents (54.6% boys and 45.4% girls), aged between 12 and 17 years (M = 15.23, SD = 1.60). The victimization (R2 = .17, p <.001) and perpetration (R2 = .20. p < .001) results showed prevalence rates higher than those of previous studies. Sex was not a differentiating factor for perpetration of dating violence, but age was: the older they were, the higher the perpetration rate. In the case of victimization, an interaction between sex and age was found. Results showed that age, sex, hostile sexism and depression were variables associated to victimization whereas age, hostile sexism and depression were associated to perpetration of dating violence

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Palbociclib has antitumour effects on Pten-deficient endometrial neoplasias.

PTEN is one of the most frequently mutated genes in human cancers. The frequency of PTEN alterations is particularly high in endometrial carcinomas. Loss of PTEN leads to dysregulation of cell division, and promotes the accumulation of cell cycle complexes such as cyclin D1-CDK4/6, which is an important feature of the tumour phenotype. Cell cycle proteins have been presented as key targets in the treatment of the pathogenesis of cancer, and several CDK inhibitors have been developed as a strategy to generate new anticancer drugs. Palbociclib (PD-332991) specifically inhibits CDK4/6, and it has been approved for use in metastatic breast cancer in combination with letrazole. Here, we used a tamoxifen-inducible Pten knockout mouse model to assess the antitumour effects of cyclin D1 knockout and CDK4/6 inhibition by palbociclib on endometrial tumours. Interestingly, both cyclin D1 deficiency and palbociclib treatment triggered shrinkage of endometrial neoplasias. In addition, palbociclib treatment significantly increased the survival of Pten-deficient mice, and, as expected, had a general effect in reducing tumour cell proliferation. To further analyse the effects of palbociclib on endometrial carcinoma, we established subcutaneous tumours with human endometrial cancer cell lines and primary endometrial cancer xenografts, which allowed us to provide more translational and predictive data. To date, this is the first preclinical study evaluating the response to CDK4/6 inhibition in endometrial malignancies driven by PTEN deficiency, and it reveals an important role of cyclin D-CDK4/6 activity in their development. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Effects of the multikinase inhibitors Sorafenib and Regorafenib in PTEN deficient neoplasias.

The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) axis is frequently dysregulated in cancer due to mutations in different nodes of the pathway or constitutive activation of receptor tyrosine kinases. Multikinase inhibitors as sorafenib and regorafenib represent a therapeutic approach for the treatment of these types of tumours. In the present study, we have evaluated the anti-tumoural effects of Sorafenib and Regorafenib on endometrial, prostate and thyroid neoplasias. Both inhibitors reduced cell viability in vitro and lead to a disruption of the PI3K/AKT/mTOR pathway. In vivo, we have demonstrated that Sorafenib and Regorafenib reduce thyroid hyperplasias induced by the loss of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), although none of the treatments eliminated the disease. Altogether, we present the first study that correlates the response to multikinase inhibitors with a specific mutation. Moreover, this is the first report characterising the response to Regorafenib in thyroid, prostate and endometrial neoplasias.

Deletion of Pten in CD45-expressing cells leads to development of T-cell lymphoblastic lymphoma but not myeloid malignancies.

Since its discovery in the late 1990s, Pten has turned out to be one of the most important tumor suppressor genes. Pten loss results in increased activation of the phosphatidylinositol 3-kinase/Akt signaling pathway, which is associated with increased proliferation, survival, and neoplastic growth. Here, we have addressed the effects of conditional deletion of Pten in hematopoietic cells by crossing Pten conditional knockout mice with a knock-in mouse expressing the Cre recombinase in the CD45 locus. CD45 is also known as leukocyte common antigen, and it is expressed in virtually all white cells and in hematopoietic stem cells. Using a reporter mouse, we demonstrate that CD45:Cre mouse displays recombinase activity in both myeloid and lymphoid cells. However, deletion of Pten in CD45-expressing cells induces development of T-cell acute lymphoblastic leukemia and lymphoma, but not other hematologic malignancies.

Combinatorial therapy using dovitinib and ICI182.780 (fulvestrant) blocks tumoral activity of endometrial cancer cells.

Mutations in fibroblast growth factor receptor 2 (FGFR2) have been recently described as a molecular-specific feature in endometrial carcinomas and the presence of activated FGFR2 mutations is associated with poor prognosis. For that reason, inhibition of FGFR2 could be a therapeutic target in the treatment of endometriod carcinomas. In this work, we investigated the antitumoral activity of dovitinib (a multiple kinase inhibitor) in human endometrial cancer cell (ECC) lines. We found that dovitinib caused cell growth arrest, loss of clonogenic growth, and cell-cycle arrest in FGFR2-mutated ECCs in in vitro and in vivo experiments. Next, we investigated the mechanistic basis of dovitinib effects. We could determine that dovitinib modified expression levels of well-known key cell-cycle regulatory proteins that induce cellular senescence. To further investigate the role of dovitinib, we analyzed its effect on estrogen receptor α (ER-α) expression. Surprisingly, we discovered that dovitinib enhances ER-α expression in FGFR2-mutant ECCs. Because blocking one signaling pathway is often not sufficient to cause total tumor regression and the effectiveness of individual inhibitors is often short-lived, we examined the impact of targeting FGFR2 with dovitinib in combination with a selective ER antagonist, fulvestrant (ICI182.780). Combination of dovitinib plus ICI182.780 resulted in a significantly higher inhibition of cell growth than dovitinib treatment alone. These findings suggest that combinatory therapies using dovitinib plus ICI182.780 treatment can be truly effective in patients with endometrial carcinomas carrying FGFR2 mutations.

An inducible knockout mouse to model the cell-autonomous role of PTEN in initiating endometrial, prostate and thyroid neoplasias.

PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. The role of PTEN in carcinogenesis has been validated by knockout mouse models. PTEN heterozygous mice develop neoplasms in multiple organs. Unfortunately, the embryonic lethality of biallelic excision of PTEN has inhibited the study of complete PTEN deletion in the development and progression of cancer. By crossing PTEN conditional knockout mice with transgenic mice expressing a tamoxifen-inducible Cre-ER(T) under the control of a chicken actin promoter, we have generated a tamoxifen-inducible mouse model that allows temporal control of PTEN deletion. Interestingly, administration of a single dose of tamoxifen resulted in PTEN deletion mainly in epithelial cells, but not in stromal, mesenchymal or hematopoietic cells. Using the mT/mG double-fluorescent Cre reporter mice, we demonstrate that epithelial-specific PTEN excision was caused by differential Cre activity among tissues and cells types. Tamoxifen-induced deletion of PTEN resulted in extremely rapid and consistent formation of endometrial in situ adenocarcinoma, prostate intraepithelial neoplasia and thyroid hyperplasia. We also analyzed the role of PTEN ablation in other epithelial cells, such as the tubular cells of the kidney, hepatocytes, colonic epithelial cells or bronchiolar epithelium, but those tissues did not exhibit neoplastic growth. Finally, to validate this model as a tool to assay the efficacy of anti-tumor drugs in PTEN deficiency, we administered the mTOR inhibitor everolimus to mice with induced PTEN deletion. Everolimus dramatically reduced the progression of endometrial proliferations and significantly reduced thyroid hyperplasia. This model could be a valuable tool to study the cell-autonomous mechanisms involved in PTEN-loss-induced carcinogenesis and provides a good platform to study the effect of anti-neoplastic drugs on PTEN-negative tumors.