75 research outputs found

    Occupational Therapists\u27 Perspectives on Psychosocial Treatment of Sexual Dysfunction with Mental Health Patients

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    Purpose: The purpose of this study is to investigate the perceptions of mental health occupational therapists about psychosocial treatment of sexual dysfunction with clients in psychiatric facilities. Methods: Using qualitative methodology, student researchers interviewed six occupational therapists practicing in psychiatric settings as part of an exploratory study into the perceptions of clinicians about treatment of sexual dysfunction with people who have mental health disabilities. Semi-structured interviews utilized open-ended questions. Electronic recording of interviews was conducted and verbatim transcripts were created. Data was analyzed and emergent codes and themes were developed. Results: Three themes emerged related to: scope of practice, perceived barriers, and client-centeredness during treatment in psychosocial practice. Discussion: The results have implications for future practice among mental health practitioners treating sexual dysfunction. Occupational therapists agree it is within the scope of practice to address sexual dysfunction as it relates to the occupational therapy practice framework. However, therapists were not congruent about the actual implementation within their respective clinical practice settings. Treatment models that may be applicable to psychosocial settings are discussed

    PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription

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    How steroid hormone receptors (SHRs) regulate transcriptional activity remains partly understood. Upon activation, SHRs bind the genome together with a co-regulator repertoire, crucial to induce gene expression. However, it remains unknown which components of the SHR-recruited co-regulator complex are essential to drive transcription following hormonal stimuli. Through a FACS-based genome-wide CRISPR screen, we functionally dissected the Glucocorticoid Receptor (GR) complex. We describe a functional cross-talk between PAXIP1 and the cohesin subunit STAG2, critical for regulation of gene expression by GR. Without altering the GR cistrome, PAXIP1 and STAG2 depletion alter the GR transcriptome, by impairing the recruitment of 3D-genome organization proteins to the GR complex. Importantly, we demonstrate that PAXIP1 is required for stability of cohesin on chromatin, its localization to GR-occupied sites, and maintenance of enhancer-promoter interactions. In lung cancer, where GR acts as tumor suppressor, PAXIP1/STAG2 loss enhances GR-mediated tumor suppressor activity by modifying local chromatin interactions. All together, we introduce PAXIP1 and STAG2 as novel co-regulators of GR, required to maintain 3D-genome architecture and drive the GR transcriptional programme following hormonal stimuli.</p

    Ribociclib induces broad chemotherapy resistance and EGFR dependency in ESR1 wildtype and mutant breast cancer

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    While endocrine therapy is highly effective for the treatment of oestrogen receptor-Ī± (ERĪ±)-positive breast cancer, a significant number of patients will eventually experience disease progression and develop treatment-resistant, metastatic cancer. The majority of resistant tumours remain dependent on ERĪ±-action, with activating ESR1 gene mutations occurring in 15ā€“40% of advanced cancers. Therefore, there is an urgent need to discover novel effective therapies that can eradicate cancer cells with aberrant ERĪ± and to understand the cellular response underlying their action. Here, we evaluate the response of MCF7-derived, CRISPR-Cas9-generated cell lines expressing mutant ERĪ± (Y537S) to a large number of drugs. We report sensitivity to numerous clinically approved inhibitors, including CDK4/6 inhibitor ribociclib, which is a standard-of-care therapy in the treatment of metastatic ERĪ±-positive breast cancer and currently under evaluation in the neoadjuvant setting. Ribociclib treatment induces senescence in both wildtype and mutant ERĪ± breast cancer models and leads to a broad-range drug tolerance. Strikingly, viability of cells undergoing ribociclib-induced cellular senescence is maintained via engagement of EGFR signalling, which may be therapeutically exploited in both wildtype and mutant ERĪ±-positive breast cancer. Our study highlights a wide-spread reduction in sensitivity to anti-cancer drugs accompanied with an acquired vulnerability to EGFR inhibitors following CDK4/6 inhibitor treatmen

    Genome Sequence of Fusobacterium nucleatum Subspecies Polymorphum ā€” a Genetically Tractable Fusobacterium

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    Fusobacterium nucleatum is a prominent member of the oral microbiota and is a common cause of human infection. F. nucleatum includes five subspecies: polymorphum, nucleatum, vincentii, fusiforme, and animalis. F. nucleatum subsp. polymorphum ATCC 10953 has been well characterized phenotypically and, in contrast to previously sequenced strains, is amenable to gene transfer. We sequenced and annotated the 2,429,698 bp genome of F. nucleatum subsp. polymorphum ATCC 10953. Plasmid pFN3 from the strain was also sequenced and analyzed. When compared to the other two available fusobacterial genomes (F. nucleatum subsp. nucleatum, and F. nucleatum subsp. vincentii) 627 open reading frames unique to F. nucleatum subsp. polymorphum ATCC 10953 were identified. A large percentage of these mapped within one of 28 regions or islands containing five or more genes. Seventeen percent of the clustered proteins that demonstrated similarity were most similar to proteins from the clostridia, with others being most similar to proteins from other gram-positive organisms such as Bacillus and Streptococcus. A ten kilobase region homologous to the Salmonella typhimurium propanediol utilization locus was identified, as was a prophage and integrated conjugal plasmid. The genome contains five composite ribozyme/transposons, similar to the CdISt IStrons described in Clostridium difficile. IStrons are not present in the other fusobacterial genomes. These findings indicate that F. nucleatum subsp. polymorphum is proficient at horizontal gene transfer and that exchange with the Firmicutes, particularly the Clostridia, is common

    A Critical Analysis of the Food Industry and Proposed Local Solutions

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    A Critical Analysis of the Food Industry and Proposed Local Solutions The agriculture industry has consequences on the environment and human health through the production, consumption, transportation and disposal processes. By eating locally and seasonally, communities can help mitigate these consequences. We used three approaches to explore how to mitigate the negative consequences of industrial agriculture at a local level: a community garden, informational website, and a community outreach event. These initiatives aim to promote conscious purchasing, consumption, and disposal of food on a local scale. By using the Logan Community in Spokane, WA as a case study, we hypothesized that bottom up approaches within local communities can be used to address large scale problems. Through these approaches we hope to encourage environmental stewardship, human health, and community awareness in regard to industrial agriculture

    Complement factor H, vitronectin, and opticin are tyrosine-sulfated proteins of the retinal pigment epithelium.

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    Lack of tyrosine sulfation of ocular proteins results in disorganized photoreceptor structure and drastically reduced visual function, demonstrating the importance of this post-translational modification to vision. To understand the role that tyrosine sulfation plays in the function of ocular proteins, we identified some tyrosine-sulfated proteins in the retinal pigment epithelium using two independent methods, immuno-affinity column purification with an anti-sulfotyrosine specific antibody and computer-based sequence analysis of retinal pigment epithelium secretome by means of the prediction program Sulfinator. Radioactive labeling followed by thin layer electrophoresis revealed that three proteins, vitronectin, opticin, and complement factor H (CFH), were post-translationally modified by tyrosine sulfation. The identification of vitronectin and CFH as tyrosine-sulfated proteins is significant, since both are deposited in drusen in the eyes of patients with age-related macular degeneration (AMD). Furthermore, mutations in CFH have been determined to be a major risk factor in the development of AMD. Future studies that seek to understand the role of CFH in the development of AMD should take into account the role that tyrosine sulfation plays in the interaction of this protein with its partners, and examine whether modulating sulfation provides a potential therapeutic target
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