Borylation via iridium catalysed C-H activation: a new concise route to duocarmycin derivatives.

The synthesis of the ethyl ester analogue of the ultrapotent antitumour antibiotic seco-duocarmycin SA has been achieved in eleven linear steps from commercially available starting materials. The DSA alkylation subunit can be made in ten linear steps from the same precursor. The route involves C-H activation at the equivalent of the C7 position on indole leading to a borylated intermediate 9 that is stable enough for peptide coupling reactions but can be easily converted to the free hydroxyl analogue.

Diverse elements comprising studies of peer support complicate evidence synthesis.

BACKGROUND: Innovative approaches to care, such as peer support, are needed to address the substantial and frequently unmet needs of people with serious mental illnesses such as schizophrenia. Although peer support services continue to expand in mental healthcare, findings of effectiveness from systematic reviews are mixed. However, the studies evaluated in these reviews consisted of diverse elements which the review methods neglected to consider. AIMS: This review aims to demonstrate the substantial diversity in intervention components and measured outcomes among studies of peer support and lay the groundwork for more focused reviews of individual intervention components. METHODS: As part of a realist review of the literature, here we synthesize evidence in a way that examines the substantial diversity in intervention components and measured outcomes comprising studies of peer support. RESULTS: Seven categories of outcomes were represented, including recovery, symptoms and functioning, and care utilization. Importantly, seven distinct intervention components were represented in 26 studies: "being there," assistance in self-management, linkage to clinical care and community resources, social and emotional support, ongoing support, explicit utilization of shared lived experience or peer support values, and systems advocacy. Reflecting diversity in approaches, no study reported all intervention components, and no component was found among all studies. IMPLICATIONS: Peer support services constitute a category of intervention approaches far too varied to evaluate as a single entity. Results suggest intervention components deserving more focused research, including assistance in self-management, "being there," and explicit utilization of shared lived experience or peer support values. PRISMA/PROSPERO: As this article reports results from a realist review of the literature, we did not follow the PRISMA guidance which is suitable for systematic reviews. We did follow the Realist and Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) guidelines.This review was not registered on PROSPERO as it is not a systematic review.

Care integration goes Beyond Co-Location: Creating a Medical Home.

How to successfully integrate mental health and primary care remains a critically important question given the continued morbidity and early mortality of people with serious mental illness. This study investigated integration in a community mental health center (MHC) primarily treating people with SMI in a large, urban northeastern city where an on-site primary care center (PCC) was opened resulting in co-located mental health and primary care services being provided. Using focus groups and online surveys this study asked participants about their thoughts and interactions with the on-site PCC. Participants included staff from clinical, non-clinical, and leadership roles in the mental health center (MHC; PCC staff; and MHC clients who did not use the on-site PCC). MHC staff also offered their thoughts about and experiences with the on-site PCC one year and two years after the on-site PCC opened through an on-line survey. In both methods, staff reported limited awareness and expectations of the PCC in the first year. Staff indicated that successful care integration goes beyond co-location and peer health navigation can enhance integration. Finally, staff discussed desires for enhancing care integration and co-located services into a medical home that included communicating across medical records and providers at different agencies. Our results suggest that, in addition to the previously researched three C's of care integration (consultation, coordination, and collaboration), two more C's were essential to successful care integration: co-location and communication. Communication across medical records and providers at different agencies was an essential component of care integration, and co-location added increased ability to communicate across providers.

Implementing Person-Centered Recovery Planning: New England Mental Health Technology Transfer Center Learning Collaborative Evaluation Report.

Person-centered recovery planning (PCRP) has been a key aspect in mental health system transformation and delivering quality health care. Despite the mandate to deliver this practice and a growing evidence base, its implementation and understanding of implementation processes in behavioral health settings remain a challenge. New England Mental Health Technology Transfer Center (MHTTC) launched the PCRP in Behavioral Health Learning Collaborative to support agencies' implementation efforts through training and technical assistance. In an effort to explore and understand the internal implementation process changes facilitated by the learning collaborative, the authors conducted qualitative key informant interviews with the participants and the leadership of the PCRP learning collaborative. The interviews revealed the processes that are part of the PCRP implementation efforts, including staff training, changing agency policies and procedures, modifying treatment planning tools, and the structure of the electronic health records. The higher prior organizational investment and readiness for change, building staff's competencies in PCRP, leadership investment, and frontline staff buy-in act as factors that facilitate the implementation of PCRP in behavioral health settings. Our findings inform both the implementation of PCRP in behavioral health settings and future efforts of organizing multi-agency learning collaboratives to support PCRP implementation. Supplementary Information: The online version contains supplementary material available at 10.1007/s43477-023-00078-3.

Breaking through social determinants of health: Results from a feasibility study of Imani Breakthrough, a community developed substance use intervention for Black and Latinx people.

Racial and ethnic disparities in substance use intervention design, implementation, and dissemination have been recognized for years, yet few intervention programs have been designed and conducted by and for people who use substances. Imani Breakthrough is a two-phase 22-week intervention developed by the community, run by facilitators with lived experience and church members, that is implemented in Black and Latinx church settings. This community-based participatory research (CBPR) approach is a concept developed in response to a call for action from the State of Connecticut Department of Mental Health and Addiction Services (DMHAS) with funding from the Substance Abuse and Mental Health Services Administration (SAMHSA) to address rising rates of death due to opioid overdose, and other negative consequences of substance misuse. After nine months of didactic community meetings, the final design involved twelve weeks of education in a group setting related to the recovery process, including the impact of trauma and racism on substance use, and a focus on citizenship and community participation and the 8 dimensions of wellness, followed by ten weeks of mutual support, with intensive wraparound support and life coaching focused on the social determinants of health (SDOH). We found the Imani intervention was feasible and acceptable, with 42 % of participants retained at 12 weeks. In addition, in a subset of participants with complete data, we found a significant increase in both citizenship scores and dimensions of wellness from baseline to week 12, with the greatest improvements in the occupational, intellectual, financial, and personal responsibility dimensions. As drug overdose rates among Black and Latinx people who use substances continue to increase, it is imperative that we address the inequities in the SDOH that contribute to this disparity gap so that we can develop interventions tailored to the specific needs of Black and Latinx people who use drugs. The Imani Breakthrough intervention shows promise as a community-driven approach that can address these disparities and promote health equity.

Detection of endometrial cancer using tampon-based collection and methylated DNA markers.

OBJECTIVE: Alterations in DNA methylation are early events in endometrial cancer (EC) development and may have utility in EC detection via tampon-collected vaginal fluid. METHODS: For discovery, DNA from frozen EC, benign endometrium (BE), and benign cervicovaginal (BCV) tissues underwent reduced representation bisulfite sequencing (RRBS) to identify differentially methylated regions (DMRs). Candidate DMRs were selected based on receiver operating characteristic (ROC) discrimination, methylation level fold-change between cancers and controls, and absence of background CpG methylation. Methylated DNA marker (MDM) validation was performed using qMSP on DNA from independent EC and BE FFPE tissue sets. Women ≥45 years of age with abnormal uterine bleeding (AUB) or postmenopausal bleeding (PMB) or any age with biopsy-proven EC self-collected vaginal fluid using a tampon prior to clinically indicated endometrial sampling or hysterectomy. Vaginal fluid DNA was assayed by qMSP for EC-associated MDMs. Random forest modeling analysis was performed to generate predictive probability of underlying disease; results were 500-fold in-silico cross-validated. RESULTS: Thirty-three candidate MDMs met performance criteria in tissue. For the tampon pilot, 100 EC cases were frequency matched by menopausal status and tampon collection date to 92 BE controls. A 28-MDM panel highly discriminated between EC and BE (96% (95%CI 89-99%) specificity; 76% (66-84%) sensitivity (AUC 0.88). In PBS/EDTA tampon buffer, the panel yielded 96% (95% CI 87-99%) specificity and 82% (70-91%) sensitivity (AUC 0.91). CONCLUSION: Next generation methylome sequencing, stringent filtering criteria, and independent validation yielded excellent candidate MDMs for EC. EC-associated MDMs performed with promisingly high sensitivity and specificity in tampon-collected vaginal fluid; PBS-based tampon buffer with added EDTA improved sensitivity. Larger tampon-based EC MDM testing studies are warranted.

Training Male Sexual Abuse Survivors as Peer Leaders to Deliver Motivational Interviewing and Trauma-Informed Affirmative Care.

This paper provides a description and evaluation of training male sexual abuse survivors to deliver Motivational Interviewing (MI) and Motivational Interviewing with Trauma-Informed Affirmative Care (MI-AC) online to sexual and gender minority (SGM) men with sexual assault histories and depression. After a search and selection process, 26 men with lived experience of sexual abuse received MI training that included the use of role-playing, video demonstrations, and practice followed by weekly supervision while co-leading groups. Peer leaders completed several measures pre and post training, including beliefs about MI and self-reported learning of MI and satisfaction with the training. A sample of MI and MI-AC audio sessions were independently rated for adherence and competence. Peer leaders' beliefs about MI changed over time, while self-rated skill level stayed consistent. Peer leaders demonstrated good adherence to the MI and MI-AC conditions. Results suggest that men with lived experience of sexual trauma effectively learned to deliver MI and/or MI-AC to SGM male survivors in online groups. These interventions have the potential to expand the reach of limited services for this population as well as reduce their depression and assist in SGM men with histories of sexual abuse entering into formal mental health services.

Beyond Supported Housing: Correlates of Improvements in Quality of Life Among Homeless Adults with Mental Illness.

BACKGROUND: The goal of supported housing, aside from exiting homelessness, is to improve overall quality of life. The contribution of factors that enhance quality of life in supported housing programs, beyond housing itself, have not been empirically identified. METHODS: Five-year follow-up data from two arms of a randomized trial comparing case management with and without housing vouchers (n = 278) were examined to identify correlates of improved quality of life, beyond housing resources. RESULTS: Access to a housing contributed to 4% of the variance in improved quality of life. Improvement in psychiatric symptoms, alcohol and drug use, employment, total income, and social support were associated with an additional 34-43% of variance in improved quality of life above and beyond housing. CONCLUSION: Improvements in quality of life were more strongly associated with improvements in mental health and other aspects of social well-being than housing alone.

Clozapine Reduces Recurrent Suicidal and Self-Injurious Behavior in Treatment-Refractory Incarcerated Individuals.

This retrospective review examines clozapine's effects on treatment-refractory incarcerated individuals (N = 23) with recurrent thoughts of self-harm and/or self-injurious behavior. Emergent suicide risk assessments and days on suicide watch were assessed for the 3 months pre- and post-clozapine treatment. Total suicide assessments fell from 73 pre- to 14 post-clozapine, with a median of 2 assessments (interquartile range [IQR]: 1,5) pre-clozapine compared with 0 (IQR: 0,1) post-clozapine (p < 0.0001). Total days on suicide watch decreased from 104 days pre- to 32 post-clozapine, with a median of 3 days (IQR: 0,9) pre-clozapine compared with 0 (IQR: 0,0) post-clozapine (p = 0.0012). Emergency room visits and medical hospitalizations decreased substantially for all months of treatment. Clozapine treatment was associated with marked reductions in self-injurious thoughts and behaviors in high-risk incarcerated individuals.

Methylated DNA markers for plasma detection of ovarian cancer: Discovery, validation, and clinical feasibility.

OBJECTIVE: Aberrant DNA methylation is an early event in carcinogenesis which could be leveraged to detect ovarian cancer (OC) in plasma. METHODS: DNA from frozen OC tissues, benign fallopian tube epithelium (FTE), and buffy coats from cancer-free women underwent reduced representation bisulfite sequencing (RRBS) to identify OC MDMs. Candidate MDM selection was based on receiver operating characteristic (ROC) discrimination, methylation fold change, and low background methylation among controls. Blinded biological validation was performed using methylated specific PCR on DNA extracted from independent OC and FTE FFPE tissues. MDMs were tested using Target Enrichment Long-probe Quantitative Amplified Signal (TELQAS) assays in pre-treatment plasma from women newly diagnosed with OC and population-sampled healthy women. A random forest modeling analysis was performed to generate predictive probability of disease; results were 500-fold in silico cross-validated. RESULTS: Thirty-three MDMs showed marked methylation fold changes (10 to >1000) across all OC subtypes vs FTE. Eleven MDMs (GPRIN1, CDO1, SRC, SIM2, AGRN, FAIM2, CELF2, RIPPLY3, GYPC, CAPN2, BCAT1) were tested on plasma from 91 women with OC (73 (80%) high-grade serous (HGS)) and 91 without OC; the cross-validated 11-MDM panel highly discriminated OC from controls (96% (95% CI, 89-99%) specificity; 79% (69-87%) sensitivity, and AUC 0.91 (0.86-0.96)). Among the 5 stage I/II HGS OCs included, all were correctly identified. CONCLUSIONS: Whole methylome sequencing, stringent filtering criteria, and biological validation yielded candidate MDMs for OC that performed with high sensitivity and specificity in plasma. Larger plasma-based OC MDM studies, including testing of pre-diagnostic specimens, are warranted.

Developing and establishing the psychometric properties of the Strathclyde Citizenship Measure: A new measure for health and social care practice and research.

There has been increasing interest and research attention towards citizenship-based practices and care within health and social care settings. A framework for implementing citizenship-based interventions has helped support the participation in society of persons who have experienced major life disruptions. Yet, having ways to measure the impact of citizenship 'in action' within specific socio-cultural contexts has proved challenging. We report on the development of the Strathclyde Citizenship Measure (SCM) which seeks to establish a psychometrically sound measure of citizenship that is relevant to the Scottish context. We outline the three phases of developing the SCM: (1) item generation, (2) item reduction and piloting, and (3) measure validation. Having generated items for the SCM using concept mapping techniques, we piloted it with 407 participants who completed an online survey of a 60-item version of the SCM. The aims were to assess the validity of the items and reduce the number of items using principal components analysis for the final measure. This resulted in a 39 item SCM. We then sought to establish the psychometric properties of this shorter version of the SCM through testing its reliability, convergent, concurrent and discriminant validity. The 39 item SCM was administered online to 280 Scottish residents along with additional measures including the Warwick-Edinburgh Mental Well-being Scale (WEMWBS), the Depression, Anxiety and Stress Scale (DASS21), the Sense of Belonging Instrument (SOBI-A); the Big Five Personality Inventory (Shortened Version; BFI-10) and the Personal Social Capital Scale (PSCS-16). The factor structure and dimensionality of the SCM was examined using exploratory factor analysis and it was found to be reliable and valid. This paper explores the potential for the application of the SCM across health and social care settings and identifies future work to develop citizenship tools to facilitate dialogues about citizenship across health and social care practice settings.

Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis.

By limiting the nitrogen source to glutamic acid, we isolated cyclic peptides from Euglena gracilis containing asparagine and non-proteinogenic amino acids. Structure elucidation was accomplished through spectroscopic methods, mass spectrometry and chemical degradation. The euglenatides potently inhibit pathogenic fungi and cancer cell lines e.g., euglenatide B exhibiting IC50 values of 4.3 µM in Aspergillus fumigatus and 0.29 µM in MCF-7 breast cancer cells. In an unprecedented convergence of non-ribosomal peptide synthetase and polyketide synthase assembly-line biosynthesis between unicellular species and the metazoan kingdom, euglenatides bear resemblance to nemamides from Caenorhabditis elegans and inhibited both producing organisms E. gracilis and C. elegans. By molecular network analysis, we detected over forty euglenatide-like metabolites in E. gracilis, E. sanguinea and E. mutabilis, suggesting an important biological role for these natural products.

Citizens defining citizenship: A model grounded in lived experience and its implications for research, policy and practice.

Citizenship is gaining currency in health and social care internationally as a way of making sense of the lived experiences of people with major life disruptions who face exclusion, marginalisation and discrimination, but the concept is often contested, poorly defined and understood. This paper charts the development of an empirical model of citizenship within Scotland, UK. A mixed-method, community-based participatory research approach using 10 focus groups (n = 77), concept-mapping exercises (n = 45) and statement clarity and relevant ratings (n = 242) was used to develop a model of citizenship that is grounded in the lived experience of participants, which is absent from current conceptualisations of citizenship. Multidimensional scaling and hierarchical cluster analysis revealed five core domains emerging from our work: 'building relationships', 'autonomy and acceptance', 'access to services and supports', 'shared values and social roles' and 'civic rights and responsibilities' representing the personal meanings of citizenship for participants. We argue that the value of this model is that it is draws upon the personal understandings and experiences of participants who emphasised the 'banal ordinariness' of its core elements. We suggest that the model makes an original contribution by clearly illustrating the practical applicability of citizenship as a concept; thus, enhancing existing theories of citizenship. Our model highlights the interplay between the relational and structural aspects of citizenship and acknowledges the barriers that marginalised groups face in claiming their citizenship rights. It offers a call to action for policy makers and practitioners to set goals that contribute to the social inclusion of those who have experienced major life disruptions.

Treatment decision-making needs among emerging adults with early psychosis.

AIM: Many emerging adults disengage from early intervention in psychosis (EIP) services prematurely. Service disengagement may be in part due to having unresolved treatment decision-making needs about use of mental health services. A basic understanding of the decision-making needs of this population is lacking. The purpose of this qualitative study was to identify the range of treatment decisions that emerging adults face during their initial engagement in an EIP program and elucidate barriers and facilitators to decision-making. METHODS: Twenty emerging adults with early psychosis were administered semistructured interviews to capture treatment decision-making experiences during the first six months after enrolment in an EIP program. Interviews were audio-recorded and transcribed verbatim. Responses were independently coded by two authors using an integrated thematic analysis approach; differences in coding were discussed to consensus. Data analysis was facilitated using NVivo 12 Plus. RESULTS: Emerging adults identified numerous decisions faced after EIP enrolment. Decisions pertaining to life and treatment goals and to starting and continuing psychiatric medication were commonly selected as the most difficult/complicated. Decision-making barriers included not having the right amount or type of information/knowledge, social factors (e.g., lacking social support, opposition/pressure), lacking internal resources (e.g., cognitive and communication skills, self-efficacy, motivation) and unappealing options. Obtaining information/knowledge, social supports (e.g., connection/trust, learning from others' experiences, encouragement), considering personal values, and time were decision-making facilitators. CONCLUSIONS: This study informs development and optimization of interventions to support decision-making among emerging adults with early psychosis, which may promote service engagement.

Facilitating treatment engagement for early psychosis through peer-delivered decision support: intervention development and protocol for pilot evaluation.

BACKGROUND: Emerging adults with early psychosis demonstrate high rates of service disengagement from critical early intervention services. Decision support interventions and peer support have both been shown to enhance service engagement but are understudied in this population. The purposes of this article are to describe the development of a novel peer-delivered decision coaching intervention for this population and to report plans for a pilot study designed to gather preliminary data about its feasibility, acceptability, and potential impact. METHODS: The intervention was developed based on formative qualitative data and in collaboration with a diverse team of researchers, key stakeholders, and expert consultants. The pilot trial will utilize a single-group (N = 20), pre-post, convergent mixed-methods design to explore whether and how the intervention addresses decision-making needs (the primary intervention target). The impact of the intervention on secondary outcomes (e.g., engagement in the program) will also be assessed. Additionally, through observation and feedback from the peer decision coach and study participants, we will evaluate the feasibility of research and intervention procedures, and the acceptability of information and support from the peer decision coach. DISCUSSION: The peer-delivered decision coaching intervention holds promise for assisting young people with making informed and values-consistent decisions about their care, and potentially enhancing service engagement within this traditionally difficult-to-engage population. If the intervention demonstrates feasibility and acceptability, and pilot data show its potential for improving treatment decision-making, our work will also lay the foundation for a new evidence base regarding roles for peer specialists on early intervention teams. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (Identifier: NCT04532034 ) on 28 August 2020 as Temple University Protocol Record 261047, Facilitating Engagement in Evidence-Based Treatment for Early Psychosis.

Effect of Clozapine on Time Assigned to Restrictive Housing in a State Prison Population.

This study examined the effect of clozapine on time assigned to restrictive housing (RH; i.e., solitary confinement), disciplinary infractions, and assaults on custody staff among patients treated within the North Carolina prison system. Records were reviewed for patients initiated on clozapine (n = 84) over a 3.5-year period. Fifty-nine patients completed at least three consecutive months of treatment and were included in data analysis. Assigned RH days and disciplinary infractions were assessed for the periods prior to and after treatment with clozapine. Patients accumulated 13,500 RH days pretreatment and 3,560 days postclozapine initiation. There was a significant reduction in RH days with clozapine treatment (P < .05). Patients with personality disorders (n = 36) had a significant decrease in RH days (P < .05), while those with psychotic disorders (n = 23) showed a decrease with borderline significance (P = .051). There were 253 disciplinary infractions pretreatment, including 27 assaults on custody staff, and 118 infractions posttreatment, including 7 assaults; the decrease in infractions was significant in the first three months of treatment (P < .05). The mean ± SD duration of treatment was 269 ± 102 days. Expanding clozapine use in state prisons should be a high priority, as these data are consistent with reports of clozapine's benefits in community settings.

Implicit organizational bias: Mental health treatment culture and norms as barriers to engaging with diversity.

There are increased efforts to improve patient-provider relations and engagement within North American mental health systems. However, it is unclear how these innovations impact care for ethnic minorities, a group that continues to face social and health disparities. This study examined one such engagement innovation-person-centered care planning-to gain a better understanding of this overall process. We specifically explored how mental health providers trained in person-centered care planning work with their patients of Latinx and Asian backgrounds. In-depth interviews were conducted with mental health providers in community clinics, and narratives were analyzed via phenomenological methods. Findings revealed that regardless of specific practice innovations, it was providers' own embeddedness in their mental health organizational culture that became conspicuous as a determinant of care. This culture contained implicit preferences for clients considered to be ideal (e.g., are verbal, admit a problem or illness, accept services, and are individually oriented). These clients were experienced as ideal largely because they helped the system operate efficiently. Findings suggest that these organizational norms, preferences, and expectations-and bureaucratic demands for efficiency-may engender an implicit organizational bias that creates barriers for culturally different groups. These biases may also hinder practice innovations, whether patient-centered, disparities-focused, or otherwise. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Ferracyclic carbonyl complexes as anti-inflammatory agents.

Reaction of Fe(CO)4Br2 with 2-aminopyridine and 2-aminonapthalene yields ferracyclic iron(ii) complexes bearing two CO ligands. Irradiation with visible light releases these two CO molecules. Substitution of a halide in the parent complexes by thioglucose provides significantly enhanced water solublity and raises the quantum yield for CO release by around five times. The complexes show anti-inflammatory activity in a TNF assay in the dark.

Peptide directed phthalocyanine-gold nanoparticles for selective photodynamic therapy of EGFR overexpressing cancers.

Gold nanoparticles, covalently functionalised with the photosensitiser C11Pc and PEG, were actively targeted towards epidermal growth factor receptor overexpressing cancers using the peptide FITC-ßAAEYLRK. Selective phototoxicity was observed at nanomolar concentrations with minimal dark toxicity.

Understanding family perspectives on supported employment.

BACKGROUND: One integral way by which individuals in recovery pursue meaning and productivity in their lives is via employment. Unfortunately, the vast majority of individuals with serious mental illness (SMI) who express the desire to work remain unemployed. Families have the potential to play an important role in the domain of supported employment (SE), though may not have the knowledge or skills to do so. AIMS: This quantitative study aimed to better understand the perspectives of family members on the role of employment in recovery and the barriers faced by their loved ones in pursuing work. METHOD: Participants included 86 family members of individuals with SMI who were affiliated with their state NAMI Chapter and agreed to take part in an online survey. Wilcoxon signed-rank tests were used to determine meaningful differences between the highest and lowest ranked statements for each main research question. RESULTS: Family members recognize that employment is important to recovery and offers individuals with SMI a valued social role. Relative to other factors, financial independence and being employed in a competitive job were viewed as less important to recovery. The most salient barriers to employment included stable housing, need for transportation, concerns about losing benefits, low self-esteem, and medication side effects. CONCLUSIONS: While family members can appreciate the importance of SE and their loved ones' desire to work, they still tend to rank other factors as more integral to recovery. This underscores the need for additional education about the potential for employment to facilitate these other factors in recovery.