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Objective: Bipolar disorder is a chronic mental illness associated with substantial impairment in quality of life and function. Although there has been tremendous growth in understanding bipolar disorder with respect to treatments, very little study has focused on the viewpoint of affected individuals. The purpose of this study was to examine the subjective experience of illness among 19 men and women with rapid cycling bipolar disorder receiving treatment at an academic psychiatry clinic.Methods: Personal constructs of illness with respect to life-trajectory and societal reaction to the individual, specifically the issue of stigma, were evaluated using a semistructured, open-ended anthropological interview.Results: Participants perceived bipolar disorder as a disease with biologic underpinnings. Stigma was a major issue for all individuals. In common with individuals without serious mental illness, individuals with bipolar disorder work at mastering developmental tasks appropriate for their life stage. At times, younger individuals appeared to have difficulty separating their own identity from the effects of illness. For older individuals with bipolar disorder, life was perceived to be disrupted by bipolar disorder, with early plans and dreams often "derailed."Conclusion: Although bipolar disorder may severely alter an individual's planned life trajectory, accomplishment of life goals can at least partially offset the sense of loss that is often seen in bipolar illness. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Menopause is an important life event that has not yet been well characterized among women with severe mental illness. Our goal was to evaluate menopause-related quality of life among severely mentally ill women. METHOD: We conducted a cross-sectional assessment of perimenopausal and postmenopausal women, ages 45-55, diagnosed with schizophrenia/schizoaffective disorder, bipolar disorder, or major depression, who were receiving inpatient or outpatient psychiatric care. Women were compared regarding menopausal symptoms and quality of life using the Menopause Specific Quality of Life Scale (MENQOL). RESULTS: Women with severe mental illnesses who were peri- and post-menopausal experienced considerable vasomotor, physical, sexual, and psychosocial symptoms related to menopause. On seven of 29 MENQOL items, women with major depression reported problems significantly more often than women with other serious mental illnesses. CONCLUSIONS: This preliminary study indicates that psychiatrists and other physicians should consider the frequency and overlap of menopausal and psychiatric symptoms among women with serious mental illness in this age group. [ABSTRACT FROM AUTHOR]

To identify cancer-associated gene regulatory changes, we generated single-cell chromatin accessibility landscapes across eight tumor types as part of The Cancer Genome Atlas. Tumor chromatin accessibility is strongly influenced by copy number alterations that can be used to identify subclones, yet underlying cis-regulatory landscapes retain cancer type-specific features. Using organ-matched healthy tissues, we identified the "nearest healthy" cell types in diverse cancers, demonstrating that the chromatin signature of basal-like-subtype breast cancer is most similar to secretory-type luminal epithelial cells. Neural network models trained to learn regulatory programs in cancer revealed enrichment of model-prioritized somatic noncoding mutations near cancer-associated genes, suggesting that dispersed, nonrecurrent, noncoding mutations in cancer are functional. Overall, these data and interpretable gene regulatory models for cancer and healthy tissue provide a framework for understanding cancer-specific gene regulation.

Increased drug resistance has reduced efficiency of chemotherapic drugs such as Doxorubicin (Dox). Scrophularia amplexicaulis (Scr) is one of the most important medicinal plants in Iran that has anti-cancer activity. The aim of this study was to investigate a novel approach to enhance therapeutic efficacy of Dox (as a chemotherapeutic agent) by co-administration of Scr (as a bioactive herbal compound) in gastric cancer treatment. In the present study, effects of Dox, Scr, and their combinations (Scr-Dox) were evaluated on viability and proliferation of two gastric cancer cell lines (AGS and MKN28). Moreover, morphological changes, invasion, migration, colony formation, and apoptosis rate in the treated cancer cells were evaluated. Expression of BAX, BCL2, SAMC, SURVIVIN, CASP9, P53, MMP9, and MMP2 in the treated cancer cells and untreated controls were evaluated by Real-Time PCR method. Treatments of cancer cells by Scr, Dox, and Scr-Dox significantly decreased proliferation, invasion, migration, and colony formation of gastric cancer cells. Treatments of cancer cells by Scr, Dox, and Scr-Dox significantly increased apoptosis rate as well as decreased cells mobility through modification of apoptosis- and metastasis-related genes expression. However, anti-cancer activity of Scr-Dox combination was significantly more than Scr and Dox treatments alone. In general, we demonstrated that Scr-Dox combination therapy exerts more profound anti-cancer effects on AGS and MKN28 cell lines than Scr and Dox monotherapy., (© 2023 Wiley Periodicals LLC.)

Objectives: Dementia is a growing health concern. Persons with dementia experience higher levels of anxiety and depression, which correlates with poorer quality of life, disability and hospitalization. This is one of the few studies to use a longitudinal design to assess the impact of expressed emotion (EE) on well-being in dementia over time., Methods: Sixty-one people with dementia and their main informal caregiver were recruited from memory services. Caregiver EE was coded from a Camberwell Family Interview conducted at time one. Person with dementia's outcome measures (quality of life, depression and anxiety) were collected at time one and at 6-months follow-up., Results: Caregiver high EE was associated with higher levels of depression in people with dementia and greater anxiety at follow-up. Emotional over involvement predicted greater anxiety and critical comments predicted greater depression. Low EE appeared to have a protective effect on well-being in people with dementia. People with dementia with low EE caregivers experienced a small reduction in depression and anxiety over time, whereas those with high-EE caregivers maintained baseline levels of depression and anxiety., Conclusions: Caregiver high EE is associated with poorer psychological outcomes for people with dementia over time. Psychological therapies, such as cognitive behavioural therapy informed family interventions should be used to reduce high EE within carer and person with dementia relationships., (© 2023 The Authors. British Journal of Clinical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Determining the layers of gene regulation within the innate immune response is critical to our understanding of the cellular responses to infection and dysregulation in disease. We identified a conserved mechanism of gene regulation in human and mouse via changes in alternative first exon (AFE) usage following inflammation, resulting in changes to the isoforms produced. Of these AFE events, we identified 95 unannotated transcription start sites in mice using a de novo transcriptome generated by long-read native RNA-sequencing, one of which is in the cytosolic receptor for dsDNA and known inflammatory inducible gene, Aim2 . We show that this unannotated AFE isoform of Aim2 is the predominant isoform expressed during inflammation and contains an iron-responsive element in its 5'UTR enabling mRNA translation to be regulated by iron levels. This work highlights the importance of examining alternative isoform changes and translational regulation in the innate immune response and uncovers novel regulatory mechanisms of Aim2 ., Competing Interests: ER, PJ, SC, MC, VS, RS, BS, RA, MJ, SC, SC No competing interests declared, MA holds options in Oxford Nanopore Technologies (ONT), is a paid consultant to ONT, received reimbursement for travel, accommodation and conference fees to speak at events organized by ONT,received research funding from ONT and is an inventor on 11 UC patents licensed to ONT (6,267,872, 6,465,193, 6,746,594, 6,936,433, 7,060,50, 8,500,982, 8,679,747, 9,481,908, 9,797,013, 10,059,988, and 10,081,835), AB received reimbursement for travel, accommodation and conference fees to speak at events organized by Oxford Nanopore Technologies (ONT), (© 2021, Robinson et al.)

Biological states are controlled by orchestrated transcriptional factors (TFs) within gene regulatory networks. Here we show TFs responsible for the dynamic changes of biological states can be prioritized with temporal PageRank. We further show such TF prioritization can be extended by integrating gene regulatory networks reverse engineered from multi-omics profiles, e.g. gene expression, chromatin accessibility, and chromosome conformation assays, using multiplex PageRank., Competing Interests: The authors declare no competing interests., (© 2020 The Authors.)

Introduction: Carers of persons with dementia (PWD) experience high levels of burden and distress and may use criticism in an attempt to change the behavior of PWD and thereby reduce their distress. We hypothesized that carer distress and criticism would each have an impact on the psychological well-being of the PWD and examined whether criticism mediates the association between carer distress and PWD psychological well-being., Methods: We recruited 61 persons with a recent diagnosis of dementia and their carer via U.K. dementia services and assessed at 2 time points 6 months apart. Carers completed questionnaire measures of burden and distress. We coded critical comments from a Camberwell Family Interview. PWD completed questionnaire measures of quality of life, depression, and anxiety. We conducted correlation, regression, and mediation analyses to explore the relationship between carer variables and PWD psychological outcomes and whether criticism mediated any relationship found., Results: Carer distress, carer critical comments, and PWD anxiety and depression at 6-month follow-up were all significantly correlated. Baseline carer distress predicted poorer quality of life in PWD at 6-month follow-up. The number of carer critical comments significantly ( p < .01) mediated the effect of carer distress on PWD quality of life., Discussion: Interventions addressing carer burden and distress and offering coping strategies to help them to reduce criticism of the PWD would improve the quality of life of those affected by dementia. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Significant others of people with dementia suffer high levels of burden and distress, creating the conditions for the negative attitudes and unhelpful responses described within the construct of Expressed Emotion (EE). It is not known however, whether EE then further enhances significant other burden and distress, and whether these processes operate early after symptoms of dementia have started. The current study used a longitudinal design to examine the potential influence of EE on burden and distress in significant others of people with a recent diagnosis of dementia. Sixty-one significant others of people with dementia were recruited. Significant other EE was coded from the Camberwell Family Interview. Significant other burden and distress, and relationship quality were collected through questionnaires at baseline and at 6-month follow-up. Significant other high-EE was associated with higher levels of burden and greater distress at both baseline and 6-month follow-up, when existing relationship quality was controlled for. High-EE significant others showed increases in burden and distress from baseline to follow-up not seen in low-EE significant others. Interventions aiming to modify significant other response styles and to reduce high-EE may potentially benefit significant others by reducing their levels of burden and distress. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Objectives: Expressed Emotion (EE) refers to a number of key aspects of interpersonal relationships which have been shown to relate to outcomes in relatives of people with health conditions., Design: A systematic review and meta-analysis of EE and outcomes in relatives of persons with dementia is reported. Potential research studies were identified via a search of three electronic databases; PsychINFO, MEDLINE and the Web of Science between 1960 and 2015., Results: We reviewed 12 studies investigating correlations between EE and well-being in relatives of patients with dementia. Factors hypothesised to influence EE including attributions, social support, coping strategies and relationship quality were also reviewed., Conclusion: High-EE relatives were found to have increased levels of burden (Z = 6.967, P < 0.001) and greater levels of depression (Z = 5.842, P < 0.001). Compared to low-EE relatives, high-EE relatives were more likely to attribute the patient's problems to factors that were personal to and controllable by the patient. Relatives with less social support, inefficient coping strategies and a poor relationship with the patients, were more likely to be classified as high-EE.

Steroids regulate cell proliferation, tissue development, and cell signaling via two pathways: a nuclear receptor mechanism and genome-independent signaling. Sperm activation, egg maturation, and steroid-induced anesthesia are executed via the latter pathway, the key components of which remain unknown. Here, we present characterization of the human sperm progesterone receptor that is conveyed by the orphan enzyme α/β hydrolase domain-containing protein 2 (ABHD2). We show that ABHD2 is highly expressed in spermatozoa, binds progesterone, and acts as a progesterone-dependent lipid hydrolase by depleting the endocannabinoid 2-arachidonoylglycerol (2AG) from plasma membrane. The 2AG inhibits the sperm calcium channel (CatSper), and its removal leads to calcium influx via CatSper and ensures sperm activation. This study reveals that progesterone-activated endocannabinoid depletion by ABHD2 is a general mechanism by which progesterone exerts its genome-independent action and primes sperm for fertilization., (Copyright © 2016, American Association for the Advancement of Science.)

Objective: Non-adherence to maintenance medication regimens is a major problem, limiting outcomes for many persons with bipolar disorder. The aim of this paper is to determine the most relevant aspects of adherence attitudes in a sample of bipolar patients selected for problems with adherence behavior., Methods: Among a larger sample of bipolar disorder patients participating in a prospective follow-up study (N = 140), a subsample of patients were selected for non-adherent behavior defined as missing ≥ 30% of medication during the past month (n = 27; 19.3%). Adherence attitudes were assessed with the Rating of Medication Influences scale (ROMI), a self-reported attitudinal measure assessing reasons for and against adherence. Multiple logistic regression models for non-adherence vs. adherence were estimated with each of the 19 ROMI items in the model, while controlling for sex, age, ethnicity, education, duration of illness, and substance abuse., Results: Mean score of ROMI items corresponding to reasons for treatment adherence was greater among adherent participants, whereas the mean score of ROMI items corresponding to reasons for treatment non-adherence was greater among nonadherent participants. The ROMI item identifying that the individual believes that medications are unnecessary had the strongest influence for non-adherence (p < 0.0001). This was followed by ROMI items corresponding to no perceived daily benefit (p = 0.0008), perceived change in appearance (p = 0.0057), and perceived interference with life goals (p = 0.0033). The ROMI item identifying fear of relapse was the strongest predictor for adherence (p = 0.0017)., Conclusions: Non-adherent patients with bipolar disorder differ from adherent patients with bipolar disorder on reasons for adherence and non-adherence. Utilization of tools that evaluate medication treatment attitudes, such as the ROMI or similar measures, may assist clinicians in the selection of interventions that are most likely to modify future treatment adherence.

Objective: This randomized controlled study of 164 outpatients with bipolar disorder in a community mental health center who received standardized psychoeducation (Life Goals Program [LGP]) or treatment as usual sought to determine whether there were differences between the groups in medication adherence attitudes and behaviors., Methods: Patients were randomly assigned to treatment as usual (N=80) or treatment as usual plus LGP (N=84) and were assessed at baseline and at the three-, six-, and 12-month follow-up. Primary outcomes were change in score from baseline on the Drug Attitude Inventory (DAI) and on self-reported treatment adherence behaviors (SRTAB)., Results: At baseline, there were no significant differences between the two groups. Slightly less than half (N=41, 49%) of the LGP group participated in most or all (four to six) LGP sessions, 14% (N=12) participated in one to three sessions, and 37% (N=31) did not participate in any sessions. At the 12-month follow-up there was improvement among all patients, with no significant differences between the two groups, in DAI scores, SRTAB, symptoms, psychopathology, and functional status. Greater depressive severity at baseline was associated with more negative attitudes toward treatment over time, although this finding was not significant (p=.056). Secondary analysis of persons in the LGP group found that compared with those who did not go to any LGP sessions, those with partial or full participation in LGP sessions had improved attitudes toward medication at the three- and six-month follow-up, but no difference was found between the three LGP subgroups by the 12-month follow-up., Conclusions: There were no differences between two groups in treatment attitudes at the 12-month follow-up. Low attendance rates mitigated effects on primary outcomes. Effects of LGP may become lost over time without ongoing intervention, and individuals with depression may have reduced response to LGP.

Background: Subjective experience of illness is a critical component of treatment adherence in populations with bipolar disorder (BPD). This cross-sectional analysis examined clinical and subjective variables in relation to adherence in 140 individuals with BPD receiving treatment with mood-stabilizing medication., Methods: Nonadherence was defined as missing 30% or more of medication on the Tablets Routine Questionnaire, a self-reported measure of medication treatment adherence. Adherent and nonadherent groups were compared on measures of attitudes toward illness and treatment including the Attitudes toward Mood Stabilizers Questionnaire, the Insight and Treatment Attitudes Questionnaire, the Rating of Medication Influences, and the Multidimensional Health Locus of Control Scale., Results: Except for substance abuse comorbidity, adherent individuals (n = 113, 80.7%) did not differ from nonadherent individuals (n = 27, 19.3%) on clinical variables. However, nonadherent individuals had reduced insight into illness, more negative attitudes toward medications, fewer reasons for adherence, and more perceived reasons for nonadherence compared with adherent individuals. The strongest attitudinal predictors for nonadherence were difficulties with medication routines (odds ratio = 2.2) and negative attitudes toward drugs in general (odds ratio = 2.3)., Limitations: Results interpretation is limited by cross-sectional design, self-report methodology, and sample size., Conclusions: Comorbid substance abuse, negative attitudes toward mood-stabilizing medication, and difficulty managing to take medication in the context of one's daily schedule are primary determinants of medication treatment adherence. A patient-centered collaborative model of care that addresses negative attitudes toward medication and difficulty coping with medication routines may be ideally suited to address individual adherence challenges.

This study examined concerns regarding menopause among women with schizophrenia/schizoaffective disorder (N = 30), women with bipolar disorder (N = 25), and women with major depression (N = 36). The three groups were compared regarding knowledge of menopause, expectations of effect of menopause, and menopause-related quality of life. All women had deficits in fund of knowledge regarding menopause. More than half (53.8%) agreed that they felt more stressed due to menopause or approaching menopause, and 51.6% felt that menopause has had a negative effect on their emotional state. Perceptions of menopause effect on emotional states between the three groups were similar. The top five symptoms experienced by women with serious mental illness were all problems related to psychological issues: feeling depressed (88%, N = 80), feeling anxious (88%, N = 80), feeling tired or worn out (87%, N = 79), feeling a lack of energy (86%, N = 78), and experiencing poor memory (84%, N = 76). Larger-scale studies evaluating the effects of menopause on serious mental illness are needed to clarify how menopause affects illness outcomes in women with serious mental illness.

An emerging literature suggests that a collaborative care model, in which patients are active managers of their illness within a supportive social environment, is a beneficial approach for individuals with bipolar disorder. One aspect of treatment that is often suboptimal among individuals with bipolar disorder is treatment adherence. Establishing an ideal collaborative model may offer an opportunity to enhance treatment adherence among individuals with bipolar disorder. This paper presents results from a qualitative exploration of patients' attitudes towards the collaborative care model and how individuals with bipolar disorder perceive treatment adherence within the context of the collaborative care model. All participants were actively enrolled in outpatient treatment at a Community Mental Health Center and part of a larger study that evaluated the Life Goals Program, a manual-driven structured group psychotherapy for bipolar disorder that is based on the collaborative practice model. The Life Goals Program is designed to assist individuals to participate more effectively in the management of their bipolar illness and to improve their social and work-related problems. Individuals were queried regarding their opinions on the ingredients for an effective client-provider relationship. Quantitative data were collected on baseline treatment adherence as well. Individuals treated for bipolar disorder in a community mental health clinic identified 12 key elements that they felt were critical ingredients to a positive collaborative experience with their mental health care provider. The authors conceptualized these elements around 3 emerging themes: patient-centered qualities, provider-centered qualities, and interactional qualities. Individuals with bipolar disorder perceived the ideal collaborative model as one in which the individual has specific responsibilities such as coming to appointments and sharing information, whereas the provider likewise has specific responsibilities such as keeping abreast of current "state-of-the-arf" prescribing practices and being a good listener. Treatment adherence was identified as a self-managed responsibility within the larger context of the collaborative model. Individuals with bipolar disorder in this study placed substantial emphasis on the interactional component within the patient-provider relationship, particularly with respect to times when the individual may be more symptomatic and more impaired. It is important that clinicians and care providers gather information related to patients' perceptions of the patient-provider relationship when designing or evaluating services aimed at enhancing treatment adherence.