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STUDY QUESTION Can animation videos on how to optimize the chances of pregnancy influence stress, anxiety, depression and sexual functioning of individuals trying to conceive (TTC)? SUMMARY ANSWER There were no differences between those educated to have intercourse every other day, on the fertile window and a control group (CG), and depression and sexual dysfunction significantly increased over time for all arms. WHAT IS KNOWN ALREADY Recent findings indicate that time to pregnancy can be significantly shortened by targeting the fertile period, but some reproductive care guidelines recommend instead the practice of intercourse every other day on the basis that it is less stressful to the couple. Evidence to support guidelines on how to preserve well-being and psychosocial adjustment and optimize pregnancy chances is lacking. STUDY DESIGN, SIZE, DURATION We conducted a prospective, double-blinded, three-arm randomized controlled trial between July 2016 and November 2019. Participants were randomized to either not having any stimulus (CG) or visualizing a short animated video explaining how to improve chances of pregnancy by having intercourse every other day (EOD group), or by monitoring the fertile window (FWM group). Assessments were made before the intervention (T0), and 6 weeks (T1), 6 months (T2) and 12 months after (T3), with follow-ups censored in case of pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were childless individuals of reproductive age actively TTC and not diagnosed or unaware of a condition that could prevent spontaneous pregnancy. Individuals were excluded from recruitment if they had previous children or had a condition preventing spontaneous pregnancy. Our primary outcome was stress and secondary outcomes included anxiety, depression, sexual functioning and pregnancy. Primary analyses were performed according to intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE Of the 450 randomized participants 127 were edu

Fertility awareness (FA) among young people is low. Fertility awareness interventions have been found to contribute to increase FA in the short-term. The long-term effectiveness of FA interventions on childless and presumed fertile people, committed in a heterosexual relationship and wishing to have children in the near future is not known. In a double-blind parallel randomized controlled trial conducted between 2016 and 2018, 652 childless partnered women were randomized to either watch a 5-min video about fertility (IG: 'Intervention Group') or to not receive any intervention (CG: 'Control Group'). Participants filled out an online questionnaire at the start of the study (and in the IG group immediately before intervention). They then completed the questionnaire after 1 month, 6 months and 1 year. The questionnaire assessed FA and intentions to adopt fertility-protective behaviours. In the IG, FA levels were found to increase at 1 month post-intervention. However, significant interaction effects between group and time were only found for four out of the seven FA variables at the 6-month and 1-year follow-up. No effects were found for: (i) intentions to adopt fertility-protective behaviours; or (ii) desired timing of pregnancy. These results suggest that the fertility video intervention seems to partially increase FA in the long term. Future studies should investigate the effectiveness of different intervention formats with a focus on overcoming high attrition rates.

Canine mammary carcinoma (CMC) is one of the major health threats in dogs. The oncolytic virotherapy is a promising strategy to treat canine as well as human cancer patients with non‐pathogenic replicating viruses. Here, we evaluated the antitumor activity of one lentogenic, non‐lytic Newcastle disease virus (NDV) LaSota strain expressing GFP (NDV‐GFP) on five different CMCs and one non‐tumorigenic cell line, regarding cell viability, cell death, selectivity index, morphology, global and target gene expression analysis. As evidenced by the selectivity index, all CMC cell lines were more susceptible to NDV‐GFP in comparison with the non‐tumorigenic cells (~3.1× to ~78.7×). In addition, the oncolytic effect of NDV‐GFP was more evident in more malignant CMC cells. Also, we observed an inverse association of the IFN pathway expression and the susceptibility to NDV. The downregulated genes in NDV‐GFP‐sensitive cells were functionally enriched for antiviral mechanisms by interferon and immune system pathways, demonstrating that these mechanisms are the most prominent for oncolysis by NDV. To our knowledge, this is the first description of oncolysis by an NDV strain in canine mammary cancer cells. We also demonstrated specific molecular pathways related to NDV susceptibility in these cancer cells, opening the possibility to use NDV as a therapeutic‐targeted option for more malignant CMCs. Therefore, these results urge for more studies using oncolytic NDVs, especially considering genetic editing to improve efficacy in dogs.

Canine mammary carcinoma (CMC) is one of the major health threats in dogs. The oncolytic virotherapy is a promising strategy to treat canine as well as human cancer patients with non‐pathogenic replicating viruses. Here, we evaluated the antitumor activity of one lentogenic, non‐lytic Newcastle disease virus (NDV) LaSota strain expressing GFP (NDV‐GFP) on five different CMCs and one non‐tumorigenic cell line, regarding cell viability, cell death, selectivity index, morphology, global and target gene expression analysis. As evidenced by the selectivity index, all CMC cell lines were more susceptible to NDV‐GFP in comparison with the non‐tumorigenic cells (~3.1× to ~78.7×). In addition, the oncolytic effect of NDV‐GFP was more evident in more malignant CMC cells. Also, we observed an inverse association of the IFN pathway expression and the susceptibility to NDV. The downregulated genes in NDV‐GFP‐sensitive cells were functionally enriched for antiviral mechanisms by interferon and immune system pathways, demonstrating that these mechanisms are the most prominent for oncolysis by NDV. To our knowledge, this is the first description of oncolysis by an NDV strain in canine mammary cancer cells. We also demonstrated specific molecular pathways related to NDV susceptibility in these cancer cells, opening the possibility to use NDV as a therapeutic‐targeted option for more malignant CMCs. Therefore, these results urge for more studies using oncolytic NDVs, especially considering genetic editing to improve efficacy in dogs.

To study the role of perceived threat of infertility, barriers, and facilitators in intention to anticipate childbearing, a cross-sectional study was conducted with 240 women desiring to have children and committed in a heterosexual relationship. Participants answered an online survey between July 2016 and February 2018. Results showed that perceiving infertility as a strong barrier and being willing to use fertility treatment as a facilitator fully mediated the effect of perceived threat on intention to anticipate childbearing. In conclusion, women who perceive themselves at risk of being infertile will consider, to a higher degree, infertility as a strong barrier to achieve their reproductive life plan or will report higher willingness to use fertility treatments, which in turn would increase intentions to anticipate childbearing. Since evidence showed lack of fertility awareness, intervention initiatives should target these mediators.

A plethora of data has highlighted the role of epigenetics in the development of cancer. Initiation and progression of different cancer types are associated with a variety of changes of epigenetic mechanisms, including aberrant DNA methylation, histone modifications, and miRNA expression. At the same time, advances in the available epigenetic tools allow to investigate and reverse these epigenetic changes and form the basis for the development of anticancer drugs in human oncology. Although human and canine cancer shares several common features, only recently that studies emerged investigating the epigenetic landscape in canine cancer and applying epigenetic modulators to canine cancer. This review focuses on the existing studies involving epigenetic changes in different types of canine cancer and the use of small-molecule inhibitors in canine cancer cells.

The prolonged lockdown of health services providing high-complexity fertility treatments -as currently recommended by many reproductive medicine entities- is detrimental for society as a whole, and infertility patients in particular. Globally, approximately 0.3% of all infants born every year are conceived using assisted reproductive technology (ART) treatments. By contrast, the total number of COVID-19 deaths reported so far represents approximately 1.0% of the total deaths expected to occur worldwide over the first three months of the current year. It seems, therefore, that the number of infants expected to be conceived and born -but who will not be so due to the lockdown of infertility services- might be as significant as the total number of deaths attributed to the COVID-19 pandemic. We herein propose remedies that include a prognostic-stratification of more vulnerable infertility cases in order to plan a progressive restart of worldwide fertility treatments. At a time when preventing complications and limiting burdens for national health systems represent relevant issues, our viewpoint might help competent authorities and health care providers to identify patients who should be prioritized for the continuation of fertility care in a safe environment.

The prolonged lockdown of health services providing high-complexity fertility treatments -as currently recommended by many reproductive medicine entities- is detrimental for society as a whole, and infertility patients in particular. Globally, approximately 0.3% of all infants born every year are conceived using assisted reproductive technology (ART) treatments. By contrast, the total number of COVID-19 deaths reported so far represents approximately 1.0% of the total deaths expected to occur worldwide over the first three months of the current year. It seems, therefore, that the number of infants expected to be conceived and born -but who will not be so due to the lockdown of infertility services- might be as significant as the total number of deaths attributed to the COVID-19 pandemic. We herein propose remedies that include a prognostic-stratification of more vulnerable infertility cases in order to plan a progressive restart of worldwide fertility treatments. At a time when preventing complications and limiting burdens for national health systems represent relevant issues, our viewpoint might help competent authorities and health care providers to identify patients who should be prioritized for the continuation of fertility care in a safe environment.

Targeting self-renewal and tumorigenicity has been proposed as a potential strategy against cancer stem cells (CSCs). Epigenetic proteins are key modulators of gene expression and cancer development contributing to regulation and maintenance of self-renewal and tumorigenicity. Here, we have screened a small-molecule epigenetic inhibitor library using 3D in vitro models in order to determine potential epigenetic targets associated with self-renewal and tumorigenicity in Canine Mammary Cancer (CMC) cells. We identified inhibition of BET proteins as a promising strategy to inhibit CMC colonies and tumorspheres formation. Low doses of (+)-JQ1 were able to downregulate important genes associated to self-renewal pathways such as WNT, NOTCH, Hedgehog, PI3K/AKT/mTOR, EGF receptor and FGF receptor in CMC tumorspheres. In addition, we observed downregulation of ZEB2, a transcription factor important for the maintenance of self-renewal in canine mammary cancer cells. Furthermore, low doses of (+)-JQ1 were not cytotoxic in CMC cells cultured in 2D in vitro models but induced G2/M cell cycle arrest accompanied by upregulation of G2/M checkpoint-associated genes including BTG2 and CCNG2. Our work indicates the BET inhibition as a new strategy for canine mammary cancers by modulating the self-renewal phenotype in tumorigenic cells such as CSCs.

Rock 11 of Vale de Figueira is located in close proximity to the water line of the left bank of the Vale Figueira steam (a tributary of the river Sabor, which in turn is a tributary of the river Douro). Engraved at two distinct moments in time; the older engravings are composed of abstract motifs created by incision, and the later, pecked motifs, represent two di erent types of weapon, a set of three daggers and a halberd. is iconography, currently rare in the rock art of the eastern Trás-os-Montes, seems to correlate, based on the analysis of references and recorded copies located in other zones of the Iberian Peninsula, with the moment of transition between the 3rd and 2nd Millennium BC, and possibly extends to the 3rd quarter of this last millennium. is corresponds to a time when changes to settlement and burial patterns seem to reflect a new ideology, associated with the cult of power, the individual and the warrior., A rocha 11 de Vale de Figueira foi descoberta na margem esquerda da Ribeira de Vale da Figueira, a uente direta da margem direita do rio Sabor (bacia hidrográ- fica do rio Douro). Situada quase em cima dessa linha de água, apresentava dois painéis gravados onde se distinguiram dois momentos de gravação. Um primeiro, mais antigo, composto por motivos abstractos executados através da técnica incisa; um segundo, mais recente, realizado com base na técnica do picotado, onde se destacavam armas de dois tipos distintos, provavelmente um conjunto de três punhais e uma alabarda. Tendo por base a análise de referentes reais e de exemplares gravados situados em outras zonas da Península Ibérica, esta iconografia, bastante rara em a oramentos da facha Oriental de Trás-os-Montes, parece correlacionar- se, com o momento de transição entre o 3º e 2º Milénio a.C., podendo eventualmente prolongar-se até ao 3º quartel deste último milénio. Surge numa fase em que se verificam alterações ao nível do povoamento e do modo de enterramento, que parecem re ectir uma nova ideologia, associada ao culto do poder, do individuo e do guerreiro.

Rock 11 of Vale de Figueira is located in close proximity to the water line of the left bank of the Vale Figueira steam (a tributary of the river Sabor, which in turn is a tributary of the river Douro). Engraved at two distinct moments in time; the older engravings are composed of abstract motifs created by incision, and the later, pecked motifs, represent two di erent types of weapon, a set of three daggers and a halberd. is iconography, currently rare in the rock art of the eastern Trás-os-Montes, seems to correlate, based on the analysis of references and recorded copies located in other zones of the Iberian Peninsula, with the moment of transition between the 3rd and 2nd Millennium BC, and possibly extends to the 3rd quarter of this last millennium. is corresponds to a time when changes to settlement and burial patterns seem to reflect a new ideology, associated with the cult of power, the individual and the warrior., A rocha 11 de Vale de Figueira foi descoberta na margem esquerda da Ribeira de Vale da Figueira, a uente direta da margem direita do rio Sabor (bacia hidrográ- fica do rio Douro). Situada quase em cima dessa linha de água, apresentava dois painéis gravados onde se distinguiram dois momentos de gravação. Um primeiro, mais antigo, composto por motivos abstractos executados através da técnica incisa; um segundo, mais recente, realizado com base na técnica do picotado, onde se destacavam armas de dois tipos distintos, provavelmente um conjunto de três punhais e uma alabarda. Tendo por base a análise de referentes reais e de exemplares gravados situados em outras zonas da Península Ibérica, esta iconografia, bastante rara em a oramentos da facha Oriental de Trás-os-Montes, parece correlacionar- se, com o momento de transição entre o 3º e 2º Milénio a.C., podendo eventualmente prolongar-se até ao 3º quartel deste último milénio. Surge numa fase em que se verificam alterações ao nível do povoamento e do modo de enterramento, que parecem re ectir uma nova ideologia, associada ao culto do poder, do individuo e do guerreiro.