Nutritional, Fatty Acids, (Poly)phenols and Technological Properties of Flower Powders from Fuchsia hybrida and Alcea rosea.

Fuchsia hybrida (pena pena) and Alcea rosea L. (malvagoma) are predominant flowers in the "Horchata" infusion, a traditional beverage in southern Ecuador, to which some medicinal properties are attributed. However, there is very little published information about these two flower species. The current study aimed to obtain two dehydrated powders of these flowers and to determine their chemical composition, physicochemical and technological properties, polyphenols, and fatty acids profile. In both powdered flowers, carbohydrates predominated, with a significant content of dietary fiber and fructose. The fat content was low, mainly comprising polyunsaturated fats (62% pena pena and 52% malvagoma), with a significant presence of omega-3 (C18:3n-3,6,9) and omega-6 (C18:2n-6,9) fatty acids, showing a better n-6/n-3 balance in the malvagoma flowers. Pena pena flowers are highlighted by high anthocyanin and ellagic acid amounts, whereas malvagoma contains a high content of flavanones. In conclusion, the studied powder flowers, could be used in the formulation of new foods or as source of anthocyanins as food colorants.

Estudio descriptivo de las personas en tratamiento por adicciones que practican chemsex en la ciudad de Madrid / Descriptive analysis of chemsex users undergoing treatment for addictions in the city of Madrid

Introducción: La práctica de chemsex constituye un problema de salud pública con múltiples consecuenciaspara la salud -física, psicológica, sexual y social- de quien lo practica, tanto derivadas de las prácticassexuales de riesgo como del consumo de sustancias. El objetivo de este estudio ha sido analizar el perfilsociodemográfico, clínico, de consumo, y los antecedentes potencialmente traumáticos, de las personas entratamiento por uso de sustancias en contexto chemsex. Metodología: Estudio transversal retrospectivodescriptivo en una muestra de 529 personas en tratamiento entre el 1 de enero de 2021 y el 30 de juniode 2022 en los CAD de Madrid Salud. Resultados: Perfil sociodemográfico: Hombres Cis (99,1%), 39,1años de media, españoles (60,9%), con estudios superiores (53,9%), empleados (62,4%). Perfil clínico:VIH + (59,8%), VHC (22,2%), ITS (75,5%), diagnóstico de salud mental (56%), PrEP (45,5%). Violencias:antecedente de violencia (37,2%): violencia de odio (20,6%), violencia intrafamiliar (13,4%), violenciade pareja (10,6%), violencia sexual (10,4%); ejercicio de prostitución (10,6%). Consumo de sustancias:policonsumo (65%), mefedrona (76,9%), GHB (41,8%), anfetaminas y derivados (29,3%); vía intravenosa(49,7%), abscesos (18,1%), consumo en soledad (35,1%), sobredosis previa (17,5%). Conclusiones: Losresultados obtenidos sugieren la necesidad de recoger de forma sistemática información sobre el perfily situación de las personas en tratamiento por consumo en contexto chemsex, así como de diseñarintervenciones específicas desde la perspectiva de las adicciones, con el fin de mejorar la atención yadaptarse a las necesidades de este grupo. (AU)

Background: Chemsex has become a public health issue due to its consequences on physical,psychological, sexual, and social health. These stem not only from high-risk sexual activities, butalso from substance use. The aim of this study has been to analyse the profile of chemsex usersundergoing treatment for addiction, including sociodemographic and clinical characteristics, aswell as information about substance use and potentially traumatic events. Methods: A cross-sectional, retrospective, descriptive analysis was conducted in a sample of 529 people undergoingtreatment between 1st January 2021 and 30th June 2022 in the Centres for Addiction Treatment(CAD) of Madrid City Council. Results: Sociodemographic profile: Cis Men (99,1%), 39,1 years(mean), Spanish (60,9%), higher education (53,9%), employed (62,4%). Clinical profile: HIV +(59,8%), HCV (22,2%), STIs (75,5%), mental health diagnose (56%), PrEP (45,5%). Violence: history of violence (37,2%): hate violence (20,6%), intra-family violence (13,4%), intimate partnerviolence (10,6%), sexual violence (10,4%); sex work (10,6%). Substance use: polydrug use (65%),mephedrone (76,9%), GHB (41,8%), amphetamines and its derivatives (29,3%); intravenous use(49,7%), abscesses (18,1%), solitary drug use (35,1%), history of overdose (17,5%). Conclusion:The results obtained suggest that information about the profile and situation of chemsex usersundergoing addiction treatment be systematically collected, and specific addiction-oriented interventions be designed in order to better adapt the treatment to their needs. (AU)

PAUSA: Resultados de un programa de proximidad dirigido a personas con prácticas de chemsex en la ciudad de Madrid / PAUSA: Results of an outreach programme aimed at people with chemsex practices in the city of Madrid

Introducción: El Instituto de Adicciones de Madrid Salud (Ayuntamiento de Madrid) utiliza habitualmenteestrategias de acercamiento orientadas a diferentes grupos de población. En 2020 se impulsó un nuevoprograma de acercamiento dirigido a usuarios con prácticas de chemsex, cuyo diseño y resultadosiniciales se presentan en este trabajo. Objetivos: El programa de acercamiento PAUSA se proponeacceder a usuarios de chemsex que todavía no han demandado atención profesional, ofreciéndolesapoyo desde fases más tempranas para: reducir los riesgos de estas prácticas, programar un descansode las mismas, o facilitar un mejor acceso y enlace a los servicios públicos y comunitarios especializadosen chemsex en la ciudad de Madrid. Materiales y métodos: El diseño del programa exploró diferentesopciones de acercamiento a usuarios de chemsex en activo, incluyendo estrategias de difusión onliney a través de tarjetas y cartelería. Se ofrecieron a los usuarios dos tipos de intervenciones, breves yestructuradas. Las primeras se desarrollaron vía chat. Las segundas mediante cita programada presencialo por Skype/Zoom. Resultados: Durante el periodo de actividad analizado se realizaron un total de 739intervenciones breves por chat, beneficiando a un total de 442 usuarios. Se realizaron además un totalde 190 citas estructuradas, presenciales u online, de una hora de duración. Un total de 115 usuariosfueron derivados a centros de atención a las adicciones. La atención recibida por parte del programarecibió excelentes evaluaciones. Conclusiones: El modelo de intervención implementado en el programaPAUSA resultó efectivo para contactar con usuarios de chemsex en fases más tempranas. La captaciónonline en aplicaciones de contactos gais fue la estrategia de acercamento de mayor éxito. Los usuariosatendidos mostraron una alta aceptabilidad de este formato de intervención. (AU)

Introduction: The Institute of Addictions of Madrid Health (City Council of Madrid) routinely employsoutreach strategies aimed at different population groups. In 2020, a new outreach programme wasinitiated targeting individuals engaged in chemsex practices. This paper presents the design and initialoutcomes of this programme. Objectives: The PAUSE outreach programme aims to engage chemsexusers who have not yet sought professional help, providing them support at earlier stages to mitigatethe risks associated with these practices, introduce breaks from them, or facilitate better access andlinkage to public and community services specialised in chemsex within the city of Madrid. Materialsand Methods: The programme’s design explored various approaches to engage active chemsex users,including online dissemination strategies and through cards and posters. Users were offered twotypes of interventions: brief and structured. The former were conducted via chat, while the latterwere scheduled either for in-person meetings or through Skype/Zoom. Results: During the analysedactivity period, a total of 739 brief interventions were conducted via chat, benefiting 442 users in total.Additionally, 190 structured sessions, either in-person or online, lasting an hour each were carriedout. A total of 115 users were referred to addiction care centres. The programme’s services receivedexcellent evaluations. Conclusions: The intervention model implemented in the PAUSE programmeproved effective in reaching users engaged in chemsex during early stages. Online outreach throughgay contact apps emerged as the most successful engagement strategy. Users served demonstrated ahigh acceptability of this intervention format. (AU)

Clustering Users to Determine the Most Suitable Gamification Elements.

The use of gamification elements has extended from being a complement for a product to being integrated into multiple public services to motivate the user. The first drawback for service designers is choosing which gamification elements are appropriate for the intended audience, in addition to the possible incompatibilities between gamification elements. This work proposes a clustering technique that enables mapping different user profiles in relation to their preferred gamification elements. Additionally, by mapping the best cluster for each gamification element, it is possible to determine the preferred game genre. The article answered the following research questions: What is the relationship between the genre of the game and the element of gamification? Different user groups (profiles) for each gamification element? Results indicate that there are cases where the users are divided between those who agree or disagree. However, other elements present a great heterogeneity in the number of groups and the levels of agreement.

Contextualizing pertuzumab approval in the treatment of HER2-positive breast cancer patients.

The use of adjuvant pertuzumab in HER2-positive early-stage breast cancer has recently been approved by the EMA on the basis of data from the APHINITY trial. Accordingly, we have produced this opinion article with the aim of putting the study data in perspective against other add-on therapeutic strategies, to clarify methodological or statistical doubts about the study, and to define the population of high-risk patients with hormone receptor-negative breast cancer that we agree, in general, should be treated. With this approval, physicians must be well prepared to place the APHINITY study data in context. It is now up to each country to ratify the EMA-approved indications and to agree on reimbursement, and doctors must optimize their use based on knowledge and discussion with patients.

Cytotoxic, antioxidative, genotoxic and antigenotoxic effects of Horchata, beverage of South Ecuador.

BACKGROUND: "Horchata" is an herbal mixture infusion consumed in Southern Ecuador; 66% of its plants are anti-inflammatory medicinal plant, and 51% are analgesics. Anti-inflammatory substances can prevent carcinogenesis mediated by cytotoxic effects and can prevent DNA damage. The aim of this study was to evaluate the cytotoxicity and apoptotic/antigenotoxic effects of horchata as well as its mechanism. METHODS: Nine different varieties of horchata were prepared in the traditional way and then freeze-dried. Phytochemical screening tested for the presence of secondary metabolites using standard procedures and antioxidant activities. The cytotoxic activity was evaluated on cerebral astrocytoma (D-384), prostate cancer (PC-3), breast cancer (MCF-7), colon cancer (RKO), lung cancer (A-549), immortalized Chinese hamster ovary cells (CHO-K1), and human peripheral blood lymphocytes via a MTS assay. The pro-apoptotic effects were evaluated with Anexin V/Propidium Iodide and western blot of Bax, Bcl-2, TP53, and TP73. Induction and reduction of ROS were assessed by fluorimetry. Genotoxic and antigenotoxic effects were evaluated with a comet assay and micronuclei on binucleated cells. RESULTS: Five of nine horchatas had cytotoxic effects against D-384 while not affecting normal cells. These horchatas induce cell death by apoptosis modulated by p53/p73. In CHO-K1 cells, the horchatas decrease the damage induced by hydrogen peroxide and Mitomycin C measured in the comet and micronucleus assay respectively. CONCLUSIONS: The IC50 range of effective horchatas in D-384 was 41 to 122 µg·mL-1. This effect may be related to its use in traditional medicine (brain tonic). On the other hand, immortalized Chinese hamster ovary cells (CHO-K1) and lymphocytes did not show a cytotoxic effect. The most potent horchata induced apoptosis via a p53/p73-mediated mechanism. The horchatas present antigenotoxic properties, which may be related to the antioxidant capacity. Future studies on horchata components are necessary to understand the interactions and beneficial properties.

Implication of polycomb members Bmi-1, Mel-18, and Hpc-2 in the regulation of p16INK4a, p14ARF, h-TERT, and c-Myc expression in primary breast carcinomas.

PURPOSE: Deregulation of mammalian Polycomb group (PcG) members may contribute to human carcinogenesis. p16INK4a and p14ARF tumor suppressors, human telomerase reverse transcriptase (h-TERT), and oncoprotein c-Myc have been implicated in the regulation of the cell cycle and proliferation mediated by PcG proteins, mainly Bmi-1, in mice and in cell culture experiments. Here, we examine whether these in vitro findings can be extrapolated to the in vivo situation. EXPERIMENTAL DESIGN: We measure the expression of PcG members Bmi-1, Mel-18, and Hpc-2 and their potential targets by reverse transcription-PCR, immunostaining, and Western blotting in a series of 134 breast carcinomas and correlate the data with several clinical-pathologic variables of the tumors. RESULTS: Expression of PcG genes was variably detected, but overexpression of Bmi-1 was the most frequent PcG alteration observed. In addition, statistical direct correlation in expression level of the three PcG members was detected. A correlation between c-Myc and Bmi-1 expression levels was observed; however, there was no correlation between expression of Bmi-1 and p16INK4a, p14ARF, or h-TERT. However, expression of the other PcG members Mel-18 and Hpc-2 correlated with the cell cycle regulators. Moreover, PcG mRNA-altered expression correlated significantly with certain clinical-pathologic variables associated with poor prognosis. CONCLUSIONS: Our data suggest that the oncogenic role of Bmi-1 in human primary breast carcinomas is not determined by its capacity to inhibit INK4a/ARF proteins or to induce telomerase activity.

Analysis of the candidate tumor suppressor Ris-1 in primary human breast carcinomas.

Frequent chromosome 3 losses have been described in several tumors types, which strongly suggest the presence of one or several tumor suppressor genes. Recently, a novel candidate tumor suppressor gene termed Ris-1 (for Ras-induced senescence 1) has been identified at chromosomal position 3p21.3. Ris-1 has been proposed to participate in anti-tumor responses that resemble cellular senescence and that are elicited by oncogenes such as Ras. To analyze the role of Ris-1 as a putative tumor suppressor gene in human breast cancer, we have performed a real-time quantitative analysis of its mRNA expression in 60 patients. Moreover, we carried out a first approach to evaluate the most common inactivation mechanism that can affect expression levels of tumor suppressor genes (mutation, promoter hypermethylation and allelic losses). Furthermore, a correlation study between expression as well as inactivating mechanisms of Ris-1 and several clinico-pathological parameters of the tumors was designed, with the objective of appraising the prognostic value of Ris-1 status. Decreased expression of Ris-1 was observed in 23% of the cases and overexpressed Ris-1 was detected in 15% of the primary breast tumors. Our data showed high frequency of LOH (30%) at one of the markers used. Nevertheless, a polymorphism related with the expression levels was described. Statistically significant correlations were found between decreased Ris-1 expression and negative progesterone receptors, as well as between overexpressing Ris-1 tumors and high histological grade. Despite all these data, we conclude that the suggested role of Ris-1 as tumor suppressor gene is not evident, at least in breast cancer. Future and larger series studies in different tumor types are necessary to clarify Ris-1 function in human cancer.

The GADD45, ZBRK1 and BRCA1 pathway: quantitative analysis of mRNA expression in colon carcinomas.

GADD45 is a growth arrest-associated gene that is induced in response to DNA damage. This gene is a target for coordinate regulation by both ZBRK1 and BRCA1. A sequence within intron 3 of GADD45 supports specific assembly of the ZBRK1/BRCA1 complex. In this study, the relationships between GADD45, ZBRK1, and BRCA1 expression were investigated in colon carcinomas. mRNA expression of these three genes was analysed in 116 colon carcinomas by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Genetic and epigenetic changes that could alter expression of these genes were studied. Possible relationships between expression levels of GADD45, ZBRK1, and BRCA1, and a series of clinicopathological parameters classically associated with poor prognosis, were also examined. ZBRK1 showed a tendency towards underexpression, while GADD45 and BRCA1 were generally overexpressed. A direct relationship between these three genes was observed, with the exception of BRCA1 expression levels, similar to normal tissues, which showed a tendency to be associated with low levels of GADD45 mRNA. Concomitantly altered expression of ZBRK1 and BRCA1 was associated with GADD45 mRNA expression. Promoter hypermethylation was not observed in GADD45 or BRCA1, and no mutations in GADD45 or ZBRK1 were found in regions involved in the interaction between the GADD45 gene and the ZBRK1 and BRCA1 proteins. No clinicopathological parameter was correlated with altered GADD45 or ZBRK1 expression but there was a statistically significant relationship between BRCA1 levels and the sex of patients. In conclusion, these results suggest that this pathway, involved in the response to DNA damage, is deregulated in colon carcinomas, and concomitantly altered expression of ZBRK1 and BRCA1 has an additive effect on GADD45 regulation. This is the first study in human carcinomas to analyse the relationships between expression of GADD45, ZBRK1, and BRCA1 mRNA.