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1.
Article in English | MEDLINE | ID: mdl-38791742

ABSTRACT

Colombia hosts the largest number of refugees and migrants fleeing the humanitarian emergency in Venezuela, many of whom experience high levels of displacement-related trauma and adversity. Yet, Colombian mental health services do not meet the needs of this population. Scalable, task-sharing interventions, such as Group Problem Management Plus (Group PM+), have the potential to bridge this gap by utilizing lay workers to provide the intervention. However, the current literature lacks a comprehensive understanding of how and for whom Group PM+ is most effective. This mixed methods study utilized data from a randomized effectiveness-implementation trial to examine the mediators and moderators of Group PM+ on mental health outcomes. One hundred twenty-eight migrant and refugee women in northern Colombia participated in Group PM+ delivered by trained community members. Patterns in moderation effects showed that participants in more stable, less marginalized positions improved the most. Results from linear regression models showed that Group PM+-related skill acquisition was not a significant mediator of the association between session attendance and mental health outcomes. Participants and facilitators reported additional possible mediators and community-level moderators that warrant future research. Further studies are needed to examine mediators and moderators contributing to the effectiveness of task-shared, scalable, psychological interventions in diverse contexts.


Subject(s)
Mental Health , Refugees , Transients and Migrants , Humans , Colombia , Refugees/psychology , Female , Venezuela , Adult , Transients and Migrants/psychology , Transients and Migrants/statistics & numerical data , Middle Aged , Young Adult
2.
Glob Ment Health (Camb) ; 10: e33, 2023.
Article in English | MEDLINE | ID: mdl-37854434

ABSTRACT

A significant number of young people throughout the world are experiencing mental health concerns. Many young people will develop their first mental health concerns or will be managing their symptoms while enrolled in institutions of higher education. Although many colleges and universities are aware of the significant mental health needs among their students, the mental health and psychosocial needs of students often exceed the availability of resources and cultural and contextual barriers, such as stigma, may further impede access to care. Such gaps and barriers in mental health may lead to poor prognosis as well as negative educational and social outcomes. We propose that non-specialist delivered mental health and psychosocial interventions may play a critical role in reducing the gaps in care for students in higher education. In particular, non-specialist delivered care can complement existing specialized services to provide stepped models of care. Importantly, the adaptation and implementation of non-specialist delivered mental health and psychosocial support interventions in higher education may lead to innovative strategies for increasing access to care in this context, but may lead to adaptations that could apply to contexts outside of higher education as well.

3.
JMIR Form Res ; 7: e45749, 2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37578827

ABSTRACT

BACKGROUND: Digital tools assessing momentary parameters and offering interventions in people's daily lives play an increasingly important role in mental health research and treatment. Ecological momentary assessment (EMA) makes it possible to assess transient mental health states and their parameters. Ecological momentary interventions (EMIs) offer mental health interventions that fit well into individuals' daily lives and routines. Self-efficacy is a transdiagnostic construct that is commonly associated with positive mental health outcomes. OBJECTIVE: The aim of our study assessing mood, specific self-efficacy, and other parameters using EMA was 2-fold. First, we wanted to determine the effects of daily assessed moods and dissatisfaction with social contacts as well as the effects of baseline variables, such as depression, on specific self-efficacy in the training group (TG). Second, we aimed to explore which variables influenced both groups' positive and negative moods during the 7-day study period. METHODS: In this randomized controlled trial, we applied digital self-efficacy training (EMI) to 93 university students with elevated self-reported stress levels and daily collected different parameters, such as mood, dissatisfaction with social contacts, and specific self-efficacy, using EMA. Participants were randomized to either the TG, where they completed the self-efficacy training combined with EMA, or the control group, where they completed EMA only. RESULTS: In total, 93 university students participated in the trial. Positive momentary mood was associated with higher specific self-efficacy in the evening of the same day (b=0.15, SE 0.05, P=.005). Higher self-efficacy at baseline was associated with reduced negative mood during study participation (b=-0.61, SE 0.30, P=.04), while we could not determine an effect on positive mood. Baseline depression severity was significantly associated with lower specific self-efficacy over the week of the training (b=-0.92, SE 0.35, P=.004). Associations between higher baseline anxiety with higher mean negative mood (state anxiety: b=0.78, SE 0.38, P=.04; trait anxiety: b=0.73, SE 0.33, P=.03) and lower mean positive mood (b=-0.64, SE 0.28, P=.02) during study participation were found. Emotional flexibility was significantly enhanced in the TG. Additionally, dissatisfaction with social contacts was associated with both a decreased positive mood (b=-0.56, SE 0.15, P<.001) and an increased negative mood (b=0.45, SE 0.12, P<.001). CONCLUSIONS: This study showed several significant associations between mood and self-efficacy as well as those between mood and anxiety in students with elevated stress levels, for example, suggesting that improving mood in people with low mood could enhance the effects of digital self-efficacy training. In addition, engaging in 1-week self-efficacy training was associated with increased emotional flexibility. Future work is needed to replicate and investigate the training's effects in other groups and settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05617248; https://clinicaltrials.gov/study/NCT05617248.

4.
Psychol Psychother ; 96(4): 849-867, 2023 12.
Article in English | MEDLINE | ID: mdl-37294035

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has propelled a global paradigm shift in how psychological support is delivered. Remote delivery, through phone and video calls, is now commonplace around the world. However, most adoption of remote delivery methods is occurring without any formal training to ensure safe and effective care. OBJECTIVE: The purpose of this applied qualitative study was to determine practitioners' experiences of rapidly adapting to deliver psychological support remotely during COVID-19. DESIGN: We used a pragmatic paradigm and applied approach to gain perspectives related to the feasibility and perceived usefulness of synchronous remote psychological support, including views on how practitioners can be prepared. METHODS: Key informant interviews were conducted remotely with 27 specialist and non-specialist practitioners in Nepal, Perú and the USA. Interviewees were identified through purposeful sampling. Data were analysed using framework analysis. RESULTS: Respondents revealed three key themes: (i) Remote delivery of psychological support raises unique safety concerns and interference with care, (ii) Remote delivery enhances skills and expands opportunities for delivery of psychological support to new populations, and (iii) New training approaches are needed to prepare specialist and non-specialist practitioners to deliver psychological support remotely. CONCLUSIONS: Remote psychological support is feasible and useful for practitioners, including non-specialists, in diverse global settings. Simulated remote role plays may be a scalable method for ensuring competency in safe and effective remotely-delivered care.


Subject(s)
COVID-19 , Humans , United States , Pandemics , Nepal , Peru , Counseling
5.
Cognit Ther Res ; : 1-8, 2023 May 02.
Article in English | MEDLINE | ID: mdl-37363751

ABSTRACT

Purpose: Manipulating perceived self-efficacy can mitigate the negative impact of trauma and increase ability to adapt to stress. It is possible that a similar domain-based manipulation aimed at anxiety around the pandemic might mitigate the negative mental health impact of COVID-19. The current experimental study assessed whether a self-efficacy induction would be effective in reducing COVID-19 distress. Methods: Participants were randomized to a self-efficacy autobiographical memory induction or control condition. We hypothesized that individuals in the self-efficacy group would exhibit lower levels of fear on an implicit measure of emotional states following exposure to COVID-19-related stimuli. Results: A significant increase in general self-efficacy and self-confidence was found in the self-efficacy group from pre- to post-induction. Individuals in the self-efficacy group had significantly lower levels of fear counts on the implicit measure of emotional states than the control group following exposure to COVID-19-related stimuli. Conclusions: Results suggest that (1) self-efficacy can be increased among individuals with high levels of COVID-19-related distress using an autobiographical memory induction and (2) doing so reduces fear processing among these individuals when exposed to COVID-19 stimuli. This is relevant for future intervention as it reveals a possible mechanism for reducing and recovering from COVID-19-related distress. Supplementary Information: The online version contains supplementary material available at 10.1007/s10608-023-10377-6.

6.
Can J Cardiol ; 39(6): 741-753, 2023 06.
Article in English | MEDLINE | ID: mdl-37030518

ABSTRACT

Approximately 15% of adult Canadians with SARS-CoV-2 infection develop lingering symptoms beyond 12 weeks after acute infection, known as post-COVID condition or long COVID. Some of the commonly reported long COVID cardiovascular symptoms include fatigue, shortness of breath, chest pain, and palpitations. Suspected long-term cardiovascular complications of SARS-CoV-2 infection might present as a constellation of symptoms that can be challenging for clinicians to diagnose and treat. When assessing patients with these symptoms, clinicians need to keep in mind myalgic encephalomyelitis/chronic fatigue syndrome, postexertional malaise and postexertional symptom exacerbation, dysautonomia with cardiac manifestations such as inappropriate sinus tachycardia, and postural orthostatic tachycardia syndrome, and occasionally mast cell activation syndrome. In this review we summarize the globally evolving evidence around management of cardiac sequelae of long COVID. In addition, we include a Canadian perspective, consisting of a panel of expert opinions from people with lived experience and experienced clinicians across Canada who have been involved in management of long COVID. The objective of this review is to offer some practical guidance to cardiologists and generalist clinicians regarding diagnostic and treatment approaches for adult patients with suspected long COVID who continue to experience unexplained cardiac symptoms.


Subject(s)
COVID-19 , Post-Acute COVID-19 Syndrome , Adult , Humans , COVID-19/complications , COVID-19/epidemiology , COVID-19/therapy , Canada/epidemiology , SARS-CoV-2 , Heart
7.
Lancet Planet Health ; 7(3): e238-e241, 2023 03.
Article in English | MEDLINE | ID: mdl-36889865

ABSTRACT

The unequal exposure to clinical conditions and other psychological responses associated with climate change and ecological degradation is due to resource access, geographical location, and other systemic factors. Ecological distress is further determined by values, beliefs, identity presentations, and group affiliations. Current models, such as climate anxiety, have made helpful distinctions between impairment and cognitive-emotional processes but obscure underlying ethical dilemmas and fundamental inequalities, restricting our understanding of accountability and the distress emerging from intergroup dynamics. In this Viewpoint, we argue that the concept of moral injury is essential because it foregrounds social position and ethics. It identifies spectrums of both agency and responsibility (guilt, shame, and anger) and powerlessness (depression, grief, and betrayal). The moral injury framework thus goes beyond an acontextual definition of wellbeing to identify how differential access to political power influences the diversity of psychological responses and conditions related to climate change and ecological degradation. A moral injury lens supports clinicians and policy makers to transform despair and stasis into care and action by delineating both the psychological and structural elements that determine the possibilities (and limits) of individual and community agency.


Subject(s)
Mental Health , Stress Disorders, Post-Traumatic , Humans , Morals , Climate Change , Social Justice
8.
Psychol Trauma ; 15(4): 547-556, 2023 May.
Article in English | MEDLINE | ID: mdl-36701538

ABSTRACT

OBJECTIVE: The study experimentally investigated shame-induced dissociation, and to what extent that process was associated with exposure to childhood maltreatment. METHOD: Using a shame-related script-driven imagery paradigm and mirror-viewing task, 50 female participants from the community recalled two shame-related and two neutral autobiographical memories, after which they listened to recordings of themselves retelling the narratives looking in a mirror or at a black curtain (i.e., mirror-viewing task). RESULTS: Shame-related memories compared to neutral memories resulted in higher rates of dissociation. The relationship between shame and dissociation was significantly moderated by experiential avoidance or avoidance of unwanted cognitive and affective reactions. In contrast to previous research, looking in the mirror and childhood maltreatment severity did not predict dissociative responses. CONCLUSIONS: The strong relationship between shame and dissociation suggests the importance of monitoring patients' affect and behavior when revisiting shame-related memories, to not reinforce dissociative reactions and inadvertently foster treatment resistance. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
Dissociative Disorders , Shame , Humans , Female , Dissociative Disorders/psychology , Auditory Perception
9.
J Psychiatr Res ; 159: 130-134, 2023 03.
Article in English | MEDLINE | ID: mdl-36708637

ABSTRACT

Social support and perceived ability to cope with trauma have been linked to severity of PTSD symptoms. While previous literature has highlighted the influence of trauma coping style on PTSD severity, data are lacking regarding factors that may moderate this association. Such information may help inform more personalized treatments for PTSD. Toward this end, we analyzed data from 100 treatment-seeking WTC responders and survivors with full or subthreshold World Trade Center (WTC)-related PTSD who completed measures of perceived ability to cope with trauma and perceived social support prior to treatment initiation. Correlation analyses revealed that higher forward-focused perceived ability to cope (r = -0.24) and perceived social support (r = -0.32) were each associated with lower severity of PTSD symptoms. In a multivariable regression analysis, perceived social support emerged as a significant moderator of the relation between forward-focused coping and overall PTSD symptom severity (ß = -0.36). Specifically, among individuals with higher forward-focused coping, those with higher social support had lower severity of symptoms than those with lower social support. Results suggest that interventions to bolster social support among trauma survivors with a forward-focusing coping style may help mitigate severity of PTSD symptoms in treatment-seeking trauma survivors with PTSD symptoms.


Subject(s)
Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/diagnosis , Adaptation, Psychological , Cognition , Social Support , Survivors
10.
Int J Pharm ; 632: 122547, 2023 Feb 05.
Article in English | MEDLINE | ID: mdl-36572264

ABSTRACT

The chemokine receptor CCR2 plays a key role in cellular migration and inflammatory processes. While tremendous progress has been made in elucidating CCR2 function and inhibition, the majority of approaches target its N-terminal domain and less is known about the function of the remaining extracellular loops and their potential as targets. Here, we used phage display to identify an antibody-derived scFv (single chain variable fragment) clone that specifically targets the second extracellular epitope of CCR2 (ECL2) for inhibition. Using in silico molecular docking, we identified six potential primary binding conformations of the novel scFv to the specified CCR2 epitope. In silico molecular dynamic analysis was used to determine conformational stability and identify protein-protein interactions. Umbrella sampling of a range of configurations with incrementally increasing separation of scFv and target generated by force pulling simulations was used to calculate binding energies. Downstream characterization by ELISA showed high binding affinity of the ECL2-scFv to CCR2. Furthermore, we showed that blocking the second extracellular loop inhibits macrophage migration and polarized macrophages towards M1 inflammatory cytokine production as potently as lipopolysaccharide (LPS). These studies highlight the applicability of epitope-specific targeting, emphasize the importance of in silico predictive modeling, and warrant further investigation into the role of the remaining epitopes of CCR2.


Subject(s)
Single-Chain Antibodies , Molecular Docking Simulation , Single-Chain Antibodies/chemistry , Epitopes , Molecular Dynamics Simulation , Molecular Conformation
11.
Psychiatr Serv ; 74(3): 292-304, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36475826

ABSTRACT

OBJECTIVE: The COVID-19 pandemic led to a rapid shift toward remote delivery of psychological interventions and transition to voice-only and video communication platforms. However, agreement is lacking on key competencies that are aligned with equitable approaches for standardized training and supervision of remote psychological intervention delivery. A rapid review was conducted to identify and describe competencies that could inform best practices of remote services delivery during and after the COVID-19 pandemic. METHODS: Scopus, MEDLINE, and PsycINFO were searched for literature published in English (2015-2021) on competencies for synchronous, remote psychological interventions that can be measured through observation. RESULTS: Of 135 articles identified, 12 met inclusion criteria. Studies targeted populations in high-income countries (11 in the United States and Canada, one in Saudi Arabia) and focused on specialist practitioners, professionals, or trainees in professional or prelicensure programs working with adult populations. Ten skill categories were identified: emergency and safety protocols for remote services, facilitating communication over remote platforms, remote consent procedures, technological literacy, practitioner-client identification for remote services, confidentiality during remote services, communication skills during remote services, engagement and interpersonal skills for remote services, establishing professional boundaries during remote services, and encouraging continuity of care during remote services. CONCLUSIONS: These 10 skills domains can offer a foundation for refinement of discrete, individual-level competencies that can be aligned with global initiatives promoting use of observational competency assessment during training and supervision programs for psychological interventions. More research is needed on identification of and agreement on remote competencies and on their evaluation.


Subject(s)
COVID-19 , Humans , United States , Pandemics , Canada
12.
Psychol Trauma ; 2022 Dec 01.
Article in English | MEDLINE | ID: mdl-36455888

ABSTRACT

OBJECTIVE: Human rights advocates investigate, document, and combat abuses of individuals and groups around the world and are routinely exposed to events that can be seen as potentially morally injurious. However, few studies have examined the unique risk factors for poor mental health outcomes among this population, and none has explored the impact of moral injury, which is particularly germane given the relevance of this concept arising from the occupational exposure to morally injurious events inherent to human rights work. METHOD: To address this deficit, we first conducted an exploratory factor analysis on a set of questions about moral injury that had previously been administered to a sample of human rights advocates. Based on this analysis, we modified and reduced these items and identified two constituent subscales. Next, we collected data on a new sample to replicate the factor structure of the reduced scale and to validate the subscales. Finally, we examined the relationship between the two subscales of the reduced moral injury scale and related concepts including posttraumatic stress disorder (PTSD), self-efficacy, and perfectionism in the original sample of human rights advocates. RESULTS: As predicted, moral injury was associated with PTSD symptom severity and, independently, with self-efficacy and perfectionism. CONCLUSIONS: The findings add to a growing body of research demonstrating the application of moral injury to civilian populations, particularly those systematically exposed to PMIEs who engage in work to address injustice and violence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

13.
PLoS One ; 17(11): e0277418, 2022.
Article in English | MEDLINE | ID: mdl-36374863

ABSTRACT

BACKGROUND: In 2017, accidents and other acts of violence were the fifth most common cause of death in Switzerland. Moreover, there are increasing numbers of refugees and asylum seekers (AS), who often exhibit distinct disease profiles from those of the natives of the host country. If these differences could be clearly identified, this might help to develop and implement strategies to prevent injuries in health care programs for refugees and asylum seekers. The aim of this study was to examine the types and characteristics of physical trauma profiles in patients from the two largest groups of AS in Switzerland-from Eastern Africa (EA) and the Middle East (ME)-who consulted a Swiss Emergency Department (ED) in 2017/2018. Furthermore, the physical trauma profiles of Swiss national (SN) patients were examined in order to explore potential differences. METHODS: Descriptive retrospective study of adult trauma patients consulting the ED of a Swiss University Hospital between 01/2017 and 12/2018. The study included 157 asylum seeking trauma patients from EA and ME were included in the study. These were matched by gender and age to 157 Swiss trauma patients consulting the ED in the study period. RESULTS: There were significant differences between the groups with respect to type of admission, level of severity, localization and mechanisms of injury. While SN had higher levels of injuries related to road traffic or work, AS had higher levels of injuries related to attempted suicide or to assault. CONCLUSIONS: There were differences between AS and the local population with respect to the characteristics and patterns of injury, so that strategies for preventing injuries and promoting health must be tailored to the target population. Moreover, the observed high rates of outpatient treatment for both groups underline the increasing role of EDs as primary care providers for the population served.


Subject(s)
Refugees , Humans , Adult , Retrospective Studies , Switzerland/epidemiology , Emergency Service, Hospital , Referral and Consultation
14.
Front Psychol ; 13: 927795, 2022.
Article in English | MEDLINE | ID: mdl-36237680

ABSTRACT

Patterns of memory sharing begin early in one's life, informing relationships, one's history, and one's sense of cultural belonging. Memory sharing among families has been the focus of research investigating the relationship between mental health and intergenerational memory. A burgeoning body of research is showing that intergenerational knowledge of one's family history is associated with positive mental health and wellbeing. However, research on the specific mechanisms and potential applications of such findings are just beginning to emerge. In particular, studies examining intergenerational storytelling point to the importance of culture and gender as critical factors underlying how stories are told and the extent to which these stories are associated with wellbeing. Such findings hold important promise for the pentation and treatment of mental health issues. As research in this area continues to evolve, the identification and characterization of factors and mechanisms underlying intergenerational family stories and wellbeing may help to guide the integration of family stories into mental health interventions.

15.
BMC Psychiatry ; 22(1): 300, 2022 04 28.
Article in English | MEDLINE | ID: mdl-35484539

ABSTRACT

BACKGROUND: Posttraumatic stress disorder (PTSD) has been hailed by some as the emblematic mental disorder of the COVID-19 pandemic, assuming that PTSD's life-threat criterion was met de facto. More plausible outcomes like adjustment disorder (AD) have been overlooked. METHODS: An online cross-sectional survey was launched in the initial stage of the pandemic using a convenience sample of 5 913 adults to compare the prevalence of COVID-related probable PTSD versus probable AD. The abridged Impact of Event Scale - Revised (IES-6) assessed the severity of trauma- and stressor-related symptoms over the previous week. Demographic and pandemic-related data (e.g., receiving a formal diagnosis of COVID-19, job loss, loss of loved one, confinement, material hardship) were collected. A Classification and Regression Tree analysis was conducted to uncover the pandemic experiences leading to clinical 'caseness'. Caseness was defined by a score > 9 on the IES-6 symptom measure and further characterized as PTSD or AD depending on whether the Peritraumatic Distress Inventory's life-threat item was endorsed or not. RESULTS: The participants were predominantly Caucasian (72.8%), women (79.2%), with a university degree (85%), and a mean age of 42.22 (SD = 15.24) years; 3 647 participants (61.7%; 95%CI [60.4, 63.0]) met the threshold for caseness. However, when perceived life-threat was accounted for, only 6.7% (95%CI [6.1, 7.4]) were classified as PTSD cases, and 55% (95%CI [53.7, 56.2]) as AD cases. Among the AD cases, three distinct profiles emerged marked by the following: (i) a worst personal pandemic experience eliciting intense fear, helplessness or horror (in the absence, however, of any life-threat), (ii) a pandemic experience eliciting sadness/grief, and (iii) worrying intensely about the safety of significant others. CONCLUSIONS: Studies considering the life-threat criterion as met de facto during the pandemic are confusing PTSD for AD on most counts. This misconception is obscuring the various AD-related idioms of distress that have emerged during the pandemic and the actual treatment needs.


Subject(s)
COVID-19 , Stress Disorders, Post-Traumatic , Adjustment Disorders/diagnosis , Adjustment Disorders/epidemiology , Adult , COVID-19/epidemiology , Cross-Sectional Studies , Female , Humans , Pandemics , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/epidemiology
16.
Emotion ; 22(6): 1148-1158, 2022 Sep.
Article in English | MEDLINE | ID: mdl-33630625

ABSTRACT

Self-efficacy is a key construct in behavioral science with significant impact on mental health and wellbeing. A growing body of work has shown that perceptions of self-efficacy can be increased through recall of autobiographical episodes (AEs) of mastery ("self-efficacy memories") in experimental settings. Doing so contributes to improvements in clinically relevant processes, such as emotion regulation and problem solving. Here we examine whether the recall of self-efficacy AEs contributes to more adaptive appraisals for personally experienced negative memories. Seventy-five healthy individuals each identified an idiosyncratic personal negative memory that was screened for emotional attributes. Participants were then asked to either recall self-efficacy (SE, n = 25) or positive (POS, n = 25) autobiographical episodes. We investigated induction effects on subsequent reappraisals of the personal negative memories. The SE induction was associated with significant reductions in distress, and subjective physiological responses as compared to the POS induction. No significant induction effects emerged in autonomic regulation. These findings suggest that recalling self-efficacy episodes may promote adaptive self-appraisals for negative memories, which in turn may contribute to recovery from stressful events and, with further research, may prove to be a useful adjunctive strategy for treatments such as CBT. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
Memory, Episodic , Cognition , Emotions/physiology , Humans , Mental Recall/physiology , Self Efficacy
17.
SSM Ment Health ; 1: 100006, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34494013

ABSTRACT

In the age of COVID-19, the Asian American community is facing a number of unique risks and barriers to mental health care. Mounting challenges-including language barriers, unemployment, racialized trauma, and anti-Asian violence-threaten the health and wellness of these communities. Yet, structural obstacles prevent Asian Americans from accessing care within the professionalized behavioral health workforce. Leveraging the resources of Asian American peer networks, collectives, and community-based organizations through a task-sharing program presents an attractive alternative for mental health care provision. Investing in task-sharing approaches to care would both address access barriers and build capacity within the Asian American community.

18.
Cancers (Basel) ; 13(15)2021 Jul 21.
Article in English | MEDLINE | ID: mdl-34359565

ABSTRACT

BACKGROUND: BRCA2 is known to be a tumor suppressor involved in homologous recombination repair and presumed to prevent genome instability in normal tissues prior to the development of tumors. Typical assessment of BRCA2 deficiency on the genome involves cell-based models using cancer cells with mixed genetic contexts, but the role in normal tissue in vivo has not been clearly demonstrated. METHODS: Using conditional deletion of Brca2 exon 11, the region containing all eight BRC repeats, in the retinal pigment epithelium and the pink-eyed unstable mouse model, we evaluate the frequency of DNA deletion events. RESULTS: In the current study, we show that conditional loss of Brca2 exon 11 results in a decreased frequency of spontaneous homologous recombination compared to wild-type mice. Of note, we observe no apparent concomitant increase in events that indicate single-strand annealing by the pink-eyed unstable mouse model. CONCLUSIONS: Therefore, our results demonstrate that BRCA2, as expected, is required for high-fidelity homologous recombination DNA repair in normal tissues, here in a tissue undergoing normal proliferation through normal development.

19.
BMC Genomics ; 22(1): 600, 2021 Aug 06.
Article in English | MEDLINE | ID: mdl-34362292

ABSTRACT

BACKGROUND: Nucleotide excision repair is the primary DNA repair mechanism that removes bulky DNA adducts such as UV-induced pyrimidine dimers. Correspondingly, genome-wide mapping of nucleotide excision repair with eXcision Repair sequencing (XR-seq), provides comprehensive profiling of DNA damage repair. A number of XR-seq experiments at a variety of conditions for different damage types revealed heterogenous repair in the human genome. Although human repair profiles were extensively studied, how repair maps vary between primates is yet to be investigated. Here, we characterized the genome-wide UV-induced damage repair in gray mouse lemur, Microcebus murinus, in comparison to human. RESULTS: We derived fibroblast cell lines from mouse lemur, exposed them to UV irradiation, and analyzed the repair events genome-wide using the XR-seq protocol. Mouse lemur repair profiles were analyzed in comparison to the equivalent human fibroblast datasets. We found that overall UV sensitivity, repair efficiency, and transcription-coupled repair levels differ between the two primates. Despite this, comparative analysis of human and mouse lemur fibroblasts revealed that genome-wide repair profiles of the homologous regions are highly correlated, and this correlation is stronger for highly expressed genes. With the inclusion of an additional XR-seq sample derived from another human cell line in the analysis, we found that fibroblasts of the two primates repair UV-induced DNA lesions in a more similar pattern than two distinct human cell lines do. CONCLUSION: Our results suggest that mouse lemurs and humans, and possibly primates in general, share a homologous repair mechanism as well as genomic variance distribution, albeit with their variable repair efficiency. This result also emphasizes the deep homologies of individual tissue types across the eukaryotic phylogeny.


Subject(s)
DNA Damage , Pyrimidine Dimers , Animals , DNA Damage/genetics , DNA Repair/genetics , Genome, Human , Humans , Primates/genetics , Ultraviolet Rays
20.
Front Psychol ; 12: 624641, 2021.
Article in English | MEDLINE | ID: mdl-34211416

ABSTRACT

Recent work on intergenerational memory has revealed a positive association between family of origin knowledge and wellbeing in adolescents. However, little is known about the generalizability of these data, as significantly less attention has focused on autobiographical memory sharing and wellbeing in historically marginalized communities. Given the high incidence of familial rejection and abandonment within the LGBTQIA + community, close relationships with individuals outside of one's family of origin, chosen families, often serve as an important source of social support. This study sought to examine the relationship between knowledge of a close non-family member and wellbeing among emerging adult sexual minority women (SMW) according to their gender presentation. A community sample from New York City comprised of heterosexual women (n = 50), masculine-presenting SMW (n = 50), and feminine presenting SMW (n = 50) completed measures associated with their knowledge of their family of origin, knowledge of a close non-family member, as well as self-reported measures of depression, emotion regulation, and socio-demographic questions. Family of origin knowledge was associated with lower levels of depression only among heterosexual women. However, heterosexual and SMW who knew more about their close non-family member reported lower levels of depression. Additionally, emotion regulation (cognitive reappraisals) mediated the relationship between knowing more about one's chosen family and lower depressive symptom severity among heterosexual women, but this relationship was only significant for SMW who were at least moderately open about their sexuality. These findings extend the literature on the benefits of memory sharing to historically marginalized communities by showing that memory sources outside of one's family of origin may be particularly important. Additionally, these data begin to shed light on potential mediating factors, such as emotion regulation and openness about one's sexual identity, that underlie the links between memory sharing and metrics of wellbeing. Taken together, in contexts in which there may not be opportunities to learn about family history from one's family of origin, it appears that access to stories from someone close outside of one's family is also associated with lower levels of depression.

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