Randomized evaluation of an online single-session intervention for minority stress in LGBTQ+ adolescents.

Background: LGBTQ+ youth face myriad adverse health outcomes due to minority stress, creating a need for accessible, mechanism-targeted interventions to mitigate these minority stress-related risk factors. We tested the effectiveness and acceptability of Project RISE, an online single-session intervention designed to ameliorate internalized stigma and improve other outcomes among LGBTQ+ youth. We hypothesized that youth assigned to RISE (versus a control) would report significantly reduced internalized stigma and increased identity pride at post-intervention and at two-week follow-up and would find RISE acceptable. Methods: We recruited adolescents nationally through Instagram advertisements in May 2022 (N = 538; M age = 15.06, SD age = 0.97). Participants were randomly assigned to RISE or an information-only control and completed questionnaires pre-intervention, immediately post-intervention, and two weeks post-intervention. Inclusion criteria included endorsing: (1) LGBTQ+ identity, (2) age 13-16, (3) English fluency (4) Internet access, and (5) subjective negative impact of LGBTQ+ stigma. Results: Relative to participants in the control condition, participants who completed RISE reported significant decreases in internalized stigma (d = -0.49) and increases in identity pride (d = 0.25) from pre- to immediately post-intervention, along with decreased internalized stigma (d = -0.26) from baseline to two-week follow-up. Participants rated both RISE and the information-only control as highly, equivalently acceptable. Conclusions: RISE appears to be an acceptable and useful online SSI for LGBTQ+ adolescents, with potential to reduce internalized stigma in both the short- and longer-term. Future directions include evaluating effects of Project RISE over longer follow-ups and in conjunction with other mental health supports.

Global longitudinal strain to predict left ventricular dysfunction in asymptomatic patients with severe mitral valve regurgitation: literature review.

The optimal treatment strategy for asymptomatic patients with severe mitral valve regurgitation (MR) and preserved left ventricular (LV) function is challenging. This manuscript reviews the available literature on the value of left ventricular global longitudinal strain (LV-GLS) in predicting LV dysfunction after mitral valve surgery in these patients and discusses its current place in the treatment strategy. Studies were identified from Cochrane Library, SCOPUS, PubMed and Web of Science up to February 2018. The domain used was MR. The determinant was LV-GLS; other methods of deformation imaging were excluded. The examined outcome was LV dysfunction after surgery. A total of 144 articles were retrieved, of which 11 publications met the inclusion criteria, including a total of 2415 patients. Ten studies showed a significant correlation between preoperative LV-GLS and LV dysfunction postoperatively; one study reported a negative correlation. These studies suggest that LV-GLS is a predictor of LV dysfunction after surgery in asymptomatic patients with chronic MR. Hence, incorporation of LV-GLS for clinical decision-making in these patients might be of additional value. Further research is needed to confirm the role of LV-GLS in postoperative patients, and additionally in asymptomatic MR patients during a 'watchful waiting' strategy.

Carcinoid heart disease: a guide for screening and timing of surgical intervention.

The cardiac manifestations of a neuroendocrine tumour are referred to as carcinoid heart disease (CaHD) and are associated with a poor prognosis. Surgical intervention is the only proven therapeutic option and may prolong survival and quality of life. No consensus has been reached internationally with regard to screening for CaHD and the optimal timing for surgery. Although limited evidence is available on this matter, a trend towards early surgery and subsequent reduced mortality has been observed. In this review we provide an overview of the current understanding and propose a protocol to guide cardiologists in the screening for CaHD and the timing of referral to a specialised surgical centre.

Anticoagulant bridging in left-sided mechanical heart valve patients.

BACKGROUND: In preparation for an invasive procedure with a high bleeding risk, patients with a mechanical heart valve temporarily have to discontinue their anticoagulant therapy and are usually bridged with either intravenous unfractionated heparin (UFH) or subcutaneous low-molecular-weight heparin (LMWH). In this study we retrospectively analyzed the safety of UFH versus LMWH as bridging strategy in left-sided mechanical heart valve patients. METHODS: We performed a retrospective multicenter study in four surgical centers in The Netherlands. Patients with a mechanical heart valve implantation bridged from January 2010 until January 2015 were included. The cumulative incidence of adverse events in the 30days following the procedure was recorded. Main outcomes were major bleeding according to International Society on Thrombosis and Haemostasis (ISTH) criteria, symptomatic thromboembolism, and mortality. RESULTS: In total, 238 (174 aortic, 42 mitral, 22 aortic+mitral) bridging episodes were included. The incidence of major bleeding was 16 (19%) events in the UFH group versus 29 (19%) events in the LMWH group (p=0.97). Incidences of thromboembolism were 2 (2.4%) versus 1 (0.6%). The incidence of death was 1 (1.2%) patient in the UFH group versus 3 (1.9%) patients in the LMWH group. More than 50% of all bleeding complications were categorized as a major bleeding. CONCLUSIONS: Bridging anticoagulation in patients with aortic and mitral mechanical valves is associated with considerable risk, but no difference was apparent between UFH and LMWH strategy. The rate of thromboembolism and death was low with either strategy and the vast majority of adverse events were bleedings.

Haemodynamic and functional consequences of the iatrogenic atrial septal defect following Mitraclip therapy.

Percutaneous MitraClip placement for treatment of severe mitral regurgitation in high surgical risk patients is a commonly performed procedure and requires a transseptal puncture to reach the left atrium. The resulting iatrogenic atrial septal defect (iASD) is not routinely closed, yet the haemodynamic and functional consequences of a persisting defect are not fully understood. Despite positive effects such as acute left atrial pressure relief, persisting iASDs are associated with negative consequences, namely significant bidirectional shunting and subsequent worse clinical outcome. Percutaneous closure of the iASD may therefore be desirable in selected cases. In this review we discuss the available literature on this matter.

Hope for prevention--perspective of the cancer advocate.

Breast and prostate cancer survivors and advocates participated as panelists with scientists in an interactive panel discussion following 2 days of scientific presentations on "Estrogens as Endogenous Carcinogens in the Breast and Prostate." Advocates raised several issues of concern and questions related to the research presented. Concerns included the following: 1) a global fear of developing either breast or prostate cancer and recurrence from these tumors, 2) a specific fear that estrogen replacement therapy could enhance the development of new breast cancers and stimulate recurrence in breast cancer survivors, and 3) a concern that researchers examining minority communities should have sensitivity to the specific culture under study and an understanding of specific research issues that are relevant in those communities. The questions raised included the following: 1) What are the implications of resistance to antiestrogen therapies and what is the appropriate sequencing of hormone therapy for longer-term benefit? 2) Can one identify women and men at risk for cancer who do not have the usual risk factors? 3) Where does the development of blood or urine tests to screen for cancer currently stand? 4) Can research findings be translated into effective therapies more rapidly? 5) Can the status of this translational process be communicated to the public in a meaningful way by breaking down language barriers? 6) What means are available to develop more creative ways to fund pilot studies that do not require preliminary data and to create new funding mechanisms to respond to the needs of scientists, particularly those that work collaboratively from multiple institutions and multidisciplines? 7) How can the need for increased emphasis on and visibility for prostate cancer be communicated? Following the interactive dialogue, scientists and advocates suggested more collaborative research with sustained funding avenues, continued dialogue and collaboration between scientists and advocates, and more collaborative research groups like the Cancer Cube.

Steric bulk at cycloartenol synthase position 481 influences cyclization and deprotonation.

Cycloartenol synthase converts oxidosqualene to the pentacyclic sterol precursor cycloartenol. An Arabidopsis thaliana cycloartenol synthase Ile481Val mutant was previously shown to produce lanosterol and parkeol in addition to its native product cycloartenol. Experiments are described here to construct Phe, Leu, Ala, and Gly mutants at position 481 and to determine their cyclization product profiles. The Phe mutant was inactive, and the Leu mutant produced cycloartenol and parkeol. The Ala and Gly mutants formed lanosterol, cycloartenol, parkeol, achilleol A, and camelliol C. Monocycles comprise most of the Gly mutant product, showing that an alternate cyclization route can be made the major pathway by a single nonpolar mutation.

Functional cloning of an Arabidopsis thaliana cDNA encoding cycloeucalenol cycloisomerase.

Plants and certain protists use cycloeucalenol cycloisomerase (EC ) to convert pentacyclic cyclopropyl sterols to conventional tetracyclic sterols. We used a novel complementation strategy to clone a cycloeucalenol cycloisomerase cDNA. Expressing an Arabidopsis thaliana cycloartenol synthase cDNA in a yeast lanosterol synthase mutant provided a sterol auxotroph that could be genetically complemented with the isomerase. We transformed this yeast strain with an Arabidopsis yeast expression library and selected sterol prototrophs to obtain a strain that accumulated biosynthetic ergosterol. The novel phenotype was conferred by an Arabidopsis cDNA that potentially encodes a 36-kDa protein. We expressed this cDNA (CPI1) in Escherichia coli and showed by gas chromatography-mass spectrometry that extracts from this strain isomerized cycloeucalenol to obtusifoliol in vitro. The cDNA will be useful for obtaining heterologously expressed protein for catalytic studies and elucidating the in vivo roles of cyclopropyl sterols.

The essential schizosaccharomyces pombe cdc23 DNA replication gene shares structural and functional homology with the Saccharomyces cerevisiae DNA43 (MCM10) gene.

The fission yeast cdc23 gene is required for correct DNA replication: cdc23 mutants show reduced rates of DNA synthesis and become elongated after cell-cycle arrest. We have cloned the Schizosaccharomyces pombe cdc23 gene by complementation of the temperature-sensitive phenotype of cdc23-M36 and confirmed the identity of the gene by integrative mapping. Analysis of the DNA sequence reveals that cdc23 can encode a protein of 593 amino acids (Mr=67 kDa) with 22% overall identity and many structural homologies with the product of the Saccharomyces cerevisiae DNA43 (MCM10) gene which is required for correct initiation of DNA synthesis at chromosomal origins of replication. Construction of a cdc23 null allele has established that the cdc23 gene is essential for viability, with cdc23 deletion mutant spores germinating but undergoing arrest with undivided nuclei in the first or second cell cycle. The S. pombe cdc23 gene on an expression plasmid is able to complement the S. cerevisiae dna43-1 mutant. These structural and functional homologies between two distantly related species suggest that cdc23 and DNA43 may represent genes for a conserved essential eukaryotic DNA replication function.