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Despite significant social and legal progress, LGBTQ+ (lesbian, gay, bisexual, transgender, and other sexual and gender minority) populations continue to experience higher rates of mental health and substance use disorders than their heterosexual and cisgender counterparts. Effective LGBTQ+ affirmative mental health care is essential for addressing these disparities but is often limited and difficult to access. The shortage of LGBTQ+ affirmative mental health care providers results from the absence of required and accessible LGBTQ+ -focused training and technical assistance opportunities for mental health care professionals. This study evaluates the implementation of our COVID-19 adapted, completely virtual, organization- and therapist-focused training program to improve the mental health workforce's cultural competence in working with the LGBTQ+ community: the "Sexual and Gender Diversity Learning Community" (SGDLC). Guided by an expanded RE-AIM model, we used administrator and therapist feedback to assess SGDLC implementation factors to understand how it may be best translated for scaled-up promotion and widespread adoption. Assessment of the initial reach, adoption, and implementation of the SGDLC indicated that it had strong feasibility; reports on satisfaction and relevance support the SGDLC's acceptability. Maintenance could not be fully assessed from the short study follow-up period. Still, administrators and therapists expressed an intent to continue their newfound practices, a desire for continued training and technical assistance in this area, but also concerns about finding additional opportunities for this education.

Primary care paediatrics is practiced throughout the countries of Europe with different structures of health care systems and identities of care providers. The best way to guarantee that paediatricians are competently trained and provide high quality care to children and adolescents in primary care is a flexible and comprehensive training program based on practice and demonstration of acquired competencies. Entrustable professional activities represent a significant step toward improving the training and assessment of future healthcare professionals. It may constitute a model that unifies the training standards in primary care and community paediatrics.

There is growing interest in decolonizing sexual and reproductive health (SRH) and embedding cultural practices into social and medical services in Hawai'i. Wahine ("woman") Talk is a multilevel, comprehensive SRH program for female youth experiencing homelessness (YEH) led by community health, social work, and medical providers. This study examines youth and program provider perspectives of culturally based approaches that may strengthen SRH programs. The study team conducted three focus groups and ten in-depth interviews with participating youth and program providers after the program's conclusion. Youth participants were aged 14 to 22 years (M = 18.1) and of Native Hawaiian or Pacific Islander ancestry. Interview transcripts were analyzed using structured thematic analysis. The youth described feeling estranged from their ancestral cultures and suggested incorporating multiple cultural practices to enhance their connection to community, body, and land into SRH programming for YEH. They identified several ?aina ("land")--based approaches, hands-on learning, hula, and language as possible practices to weave into the program. While youth felt estranged from their ancestral cultures, they discussed Native Hawaiian and Pacific Islander health perspectives where ?aina and relationships are considered life-sustaining. Youth and program staff stressed incorporating culture respectfully, caring for the whole person, and providing trauma-informed care. Future policy, practice, and research should consider protecting and integrating Native Hawaiian conceptions of health into SRH policy and practice and include youths' cultural identities in SRH intervention development.

Abstract Objective: To explore how sources of familial encouragement are associated with breast-feeding initiation and duration among a national sample participating in the US Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Design: This study uses the 2013–2015 WIC Infant and Toddler Feeding Practices Study 2 (WIC ITFPS-2) data. Breast-feeding initiation was measured at the first month, while duration was derived from a composite of the first 13 months. The analysis used logistic and linear regression to explore the association between encouragement sources and breast-feeding outcomes. Setting: A nationally representative sample of WIC participants in the USA. Participants: WIC participants who completed the 13-month interview of the WIC ITFPS-2 (n 2807). Results: Encouragement was significantly associated with both initiation and duration. Each source of encouragement was associated with a 3·2 (95 % CI 2·8, 3·8) increase in odds of initiating breast-feeding in the unadjusted model and 3·0 (95 % CI 2·5, 3·6) increased odds, controlling for age, education, nativity, poverty status, race and ethnicity (

BackgroundStark disparities exist in maternal and child outcomes and there is a need to provide timely and accurate health information. ObjectiveIn this pilot study, we assessed the feasibility and acceptability of a health chatbot for new mothers of color. MethodsRosie, a question-and-answer chatbot, was developed as a mobile app and is available to answer questions about pregnancy, parenting, and child development. From January 9, 2023, to February 9, 2023, participants were recruited using social media posts and through engagement with community organizations. Inclusion criteria included being aged ≥14 years, being a woman of color, and either being currently pregnant or having given birth within the past 6 months. Participants were randomly assigned to the Rosie treatment group (15/29, 52% received the Rosie app) or control group (14/29, 48% received a children’s book each month) for 3 months. Those assigned to the treatment group could ask Rosie questions and receive an immediate response generated from Rosie’s knowledgebase. Upon detection of a possible health emergency, Rosie sends emergency resources and relevant hotline information. In addition, a study staff member, who is a clinical social worker, reaches out to the participant within 24 hours to follow up. Preintervention and postintervention tests were completed to qualitatively and quantitatively evaluate Rosie and describe changes across key health outcomes, including postpartum depression and the frequency of emergency room visits. These measurements were used to inform the clinical trial’s sample size calculations. ResultsOf 41 individuals who were screened and eligible, 31 (76%) enrolled and 29 (71%) were retained in the study. More than 87% (13/15) of Rosie treatment group members reported using Rosie daily (5/15, 33%) or weekly (8/15, 53%) across the 3-month study period. Most users reported that Rosie was easy to use (14/15, 93%) and provided responses quickly (13/15, 87%). The remaining issues identified included crashing of the app (8/15, 53%), and users were not satisfied with some of Rosie’s answers (12/15, 80%). Mothers in both the Rosie treatment group and control group experienced a decline in depression scores from pretest to posttest periods, but the decline was statistically significant only among treatment group mothers (P=.008). In addition, a low proportion of treatment group infants had emergency room visits (1/11, 9%) compared with control group members (3/13, 23%). Nonetheless, no between-group differences reached statistical significance at P

Wind farm flow control (WFFC) is a topic of interest at several research institutes and industry and certification agencies worldwide. For reliable performance assessment of the technology, the efficiency and the capability of the models applied to WFFC should be carefully evaluated. To address that, the FarmConners consortium has launched a common benchmark for code comparison under controlled operation to demonstrate its potential benefits, such as increased power production. The benchmark builds on available data sets from previous field campaigns, wind tunnel experiments, and high-fidelity simulations. Within that database, four blind tests are defined and 13 participants in total have submitted results for the analysis of single and multiple wakes under WFFC. Here, we present Part I of the FarmConners benchmark results, focusing on the blind tests with large-scale rotors. The observations and/or the model outcomes are evaluated via direct power comparisons at the upstream and downstream turbine(s), as well as the power gain at the wind farm level under wake steering control strategy. Additionally, wake loss reduction is also analysed to support the power performance comparison, where relevant. The majority of the participating models show good agreement with the observations or the reference high-fidelity simulations, especially for lower degrees of upstream misalignment and narrow wake sector. However, the benchmark clearly highlights the importance of the calibration procedure for control-oriented models. The potential effects of limited controlled operation data in calibration are particularly visible via frequent model mismatch for highly deflected wakes, as well as the power loss at the controlled turbine(s). In addition to the flow modelling, the sensitivity of the predicted WFFC benefits to the turbine representation and the implementation of the controller is also underlined. The FarmConners benchmark is the first of its kind to bring a wide variety of data sets, control settings, and model complexities for the (initial) assessment of farm flow control benefits. It forms an important basis for more detailed benchmarks in the future with extended control objectives to assess the true value of WFFC.

Introduction The recent approval of euthanasia in the Spanish legal code and its posible extension to psychiatric patients opens an unprecedented scenario in the Iberian country. We analize the experience of the Netherlands, a country where euthanasia has been in practice for over two decades, in order to foresee epidemiological trends that could be replicated in Spain. Objectives To review the legislation on euthanasia in Spain and the Netherlands, as well as the epidemiological data regarding euthanasia applicants affected by mental health conditions in the Netherlands, to predict future epidemiological trends in a similar population in Spain. Methods We studied the legislation on euthanasia in Spain and the Netherlands, as well as the directives of the Regional Commisions for Euthanasia in the Netherlands to analize differences and similarities between the legal codes on both countries. We also sought epidemiological data regarding the application of euthanasia on psychiatric patients in the Netherlands, gathering data from seven articles in English language obtained through a search in PubMed using the MeSH terms “Euthanasia” AND “Netherlands” and “Psychiatry”. Results Euthanasia on psychiatric patients in the Netherlands has been a practice on the rise during the last decade, despite the elevated proportion of rejected applications and the high survival rate of this patients in later longitudinal studies. Affective disorders and personality disorders stand out as major psychiatric causes between the applicants. The Spanish legislation bears important resemblance to its Dutch predecessor, but also significant differences. Conclusions The available data on the application of euthanasia on mental health patients in the Netherlands show an in increasing trend regarding the execution of this practice, specially on patients who gather distinct clinical features. The data provided by the Dutch experience could have some replication in Spain, as well as anticipate possible future ethical conflicts regarding the application of this service. Disclosure of Interest None Declared

IntroductionCopoazú seed butter [Theobroma grandiflorum (Wild ex Spreng) K. Schum] is a rich source of fatty acids and polyphenols, active substances with high antioxidant and moisturizing activities with potential applications in the cosmetic industry. Some studies have demonstrated that sun-induced skin damage is partially mediated by oxidative pathways; in fact, there is evidence for the photoprotective roles of antioxidants.MethodsWe have developed a stable emulgel-type cosmetic formulation using Copoazú seed butter at different concentrations of 5, 10, and 20% and examined the antioxidant activity and the effect of Copoazú seed butter emulgels against UV-induced epidermal damage in mice to verify its use for topical photoprotective products.Results and discussionThe antioxidant activity expressed as EC50 values varied from 8.47 ± 0.013 mg/ml to 4.53 ± 0.046 mg/ml for Copoazú seed butter emulgels. In vitro sun protection factor (SPF) assessment showed that Copoazú seed butter emulgel at 20% has the highest SPF of 11.67 ± 0.001, which is acceptable for the sunscreen products development, and these results were corroborated by the in vivo results since the mice were irradiated with UV light and treated with Copoazú seed emulgels and showed minor damage or significantly reduced the severity of the damage and were comparable with the standard photo-protector. The results showed that Copoazú seed butter is a promising compound for photoprotective formulations.

The first diastereoselective synthesis of (−)-1-epi-lentiginosine from a common chiral trans-epoxyamide derived from 2-pyridincarbaldehyde is reported. This methodology involves a sequential oxirane ring opening and intramolecular 5-exo-tet cyclization of tosylate trans-epoxyalcohol to afford a diastereomeric mixture of indolizinium salts in a one-pot fashion, followed by regio- and diastereospecific pyridinium ring reduction.

Summary: Bioinformatic analysis of 94 patient-derived xenografts (PDXs), cell lines, and organoids (PCOs) identifies three intrinsic transcriptional subtypes of metastatic castration-resistant prostate cancer: androgen receptor (AR) pathway + prostate cancer (PC) (ARPC), mesenchymal and stem-like PC (MSPC), and neuroendocrine PC (NEPC). A sizable proportion of castration-resistant and metastatic stage PC (M-CRPC) cases are admixtures of ARPC and MSPC. Analysis of clinical datasets and mechanistic studies indicates that MSPC arises from ARPC as a consequence of therapy-induced lineage plasticity. AR blockade with enzalutamide induces (1) transcriptional silencing of TP53 and hence dedifferentiation to a hybrid epithelial and mesenchymal and stem-like state and (2) inhibition of BMP signaling, which promotes resistance to AR inhibition. Enzalutamide-tolerant LNCaP cells re-enter the cell cycle in response to neuregulin and generate metastasis in mice. Combined inhibition of HER2/3 and AR or mTORC1 exhibits efficacy in models of ARPC and MSPC or MSPC, respectively. These results define MSPC, trace its origin to therapy-induced lineage plasticity, and reveal its sensitivity to HER2/3 inhibition.

The possibility of extracting useful information about the state of the lower troposphere from the surface reflections that are often detected during GPS radio occultations (GPSRO) is explored. The clarity of the reflection is quantified, and can be related to properties of the surface and the low troposphere. The reflected signal is often clear enough to show good phase coherence, and can be tracked and processed as an extension of direct non-reflected GPSRO atmospheric profiles. A profile of bending angle vs. impact parameter can be obtained for these reflected signals, characterized by impact parameters that are below the apparent horizon, and that is a continuation at low altitude of the standard non-reflected bending angle profile. If there were no reflection, these would correspond to tangent altitudes below the local surface, and in particular below the local mean sea level. A forward operator is presented, for the evaluation of the bending angle of reflected GPSRO signals, given atmospheric properties as described by a numerical weather prediction system. The operator is an extension, at lower impact parameters, of standard bending angle operators, and reproduces both the direct and reflected sections of the measured profile. It can be applied to the assimilation of the reflected section of the profile as supplementary data to the direct section. Although the principle is also applicable over land, this paper is focused on ocean cases, where the topographic height of the reflecting surface, the sea level, is better known a priori.

Abstract Background The coordination between nitrogen (N) and sulfur (S) assimilation is required to suitably provide plants with organic compounds essential for their development and growth. The N source induces the adaptation of many metabolic processes in plants; however, there is scarce information about the influence that it may exert on the functioning of S metabolism. The aim of this work was to provide an overview of N and S metabolism in oilseed rape (Brassica napus) when exposed to different N sources. To do so, plants were grown in hydroponic conditions with nitrate or ammonium as N source at two concentrations (0.5 and 1 mM). Results Metabolic changes mainly occurred in leaves, where ammonium caused the up-regulation of enzymes involved in the primary assimilation of N and a general increase in the concentration of N-compounds (NH4 +, amino acids and proteins). Similarly, the activity of key enzymes of primary S assimilation and the content of S-compounds (glutathione and glucosinolates) were also higher in leaves of ammonium-fed plants. Interestingly, sulfate level was lower in leaves of ammonium-fed plants, which was accompanied by the down-regulation of SULTR1 transporters gene expression. Conclusions The results highlight the impact of the N source on different steps of N and S metabolism in oilseed rape, notably inducing N and S assimilation in leaves, and put forward the potential of N source management to modulate the synthesis of compounds with biotechnological interest, such as glucosinolates.

Cell division cycle 6 (CDC6), an androgen receptor (AR) target gene, is implicated in regulating DNA replication and checkpoint mechanisms. CDC6 expression is increased during prostate cancer (PCa) progression and positively correlates with AR in PCa tissues. AR or CDC6 knockdown, together with AZD7762, a Chk1/2 inhibitor, results in decreased TopBP1-ATR-Chk1 signaling and markedly increased ataxia-telangiectasia-mutated (ATM) phosphorylation, a biomarker of DNA damage, and synergistically increases treatment efficacy. Combination treatment with the AR signaling inhibitor enzalutamide (ENZ) and the Chk1/2 inhibitor AZD7762 demonstrates synergy with regard to inhibition of AR-CDC6-ATR-Chk1 signaling, ATM phosphorylation induction, and apoptosis in VCaP (mutant p53) and LNCaP-C4-2b (wild-type p53) cells. CDC6 overexpression significantly reduced ENZ- and AZD7762-induced apoptosis. Additive or synergistic therapeutic activities are demonstrated in AR-positive animal xenograft models. These findings have important clinical implications, since they introduce a therapeutic strategy for AR-positive, metastatic, castration-resistant PCa, regardless of p53 status, through targeting AR-CDC6-ATR-Chk1 signaling.

Chromosomal DNA elements are organized into spatial domains within the eukaryotic nucleus. Sites undergoing DNA replication, high-level transcription, and repair of double-strand breaks coalesce into foci, although the significance and mechanisms giving rise to these dynamic structures are poorly understood. In S. cerevisiae, replication origins occupy characteristic subnuclear localizations that anticipate their initiation timing during S phase. Here, we link localization of replication origins in G1 phase with Fkh1 activity, which is required for their early replication timing. Using a Fkh1-dependent origin relocalization assay, we determine that execution of Dbf4-dependent kinase function, including Cdc45 loading, results in dynamic relocalization of a replication origin from the nuclear periphery to the interior in G1 phase. Origin mobility increases substantially with Fkh1-driven relocalization. These findings provide novel molecular insight into the mechanisms that govern dynamics and spatial organization of DNA replication origins and possibly other functional DNA elements.