Evidence for Porphyrin-Mediated Electron Transfer in the Radical SAM Enzyme HutW.

Bacteria that infect the human gut must compete for essential nutrients, including iron, under a variety of different metabolic conditions. Several enteric pathogens, including Vibrio cholerae and Escherichia coli O157:H7, have evolved mechanisms to obtain iron from heme in an anaerobic environment. Our laboratory has demonstrated that a radical S-adenosylmethionine (SAM) methyltransferase is responsible for the opening of the heme porphyrin ring and release of iron under anaerobic conditions. Furthermore, the enzyme in V. cholerae, HutW, has recently been shown to accept electrons from NADPH directly when SAM is utilized to initiate the reaction. However, how NADPH, a hydride donor, catalyzes the single electron reduction of a [4Fe-4S] cluster, and/or subsequent electron/proton transfer reactions, was not addressed. In this work, we provide evidence that the substrate, in this case, heme, facilitates electron transfer from NADPH to the [4Fe-4S] cluster. This study uncovers a new electron transfer pathway adopted by radical SAM enzymes and further expands our understanding of these enzymes in bacterial pathogens.

Evidence of Atypical Structural Flexibility of the Active Site Surrounding of an [FeFe] Hydrogenase from Clostridium beijerinkii.

[FeFe] hydrogenase from Clostridium beijerinkii (CbHydA1) is an unusual hydrogenase in that it can withstand prolonged exposure to O2 by reversibly converting into an O2-protected, inactive state (Hinact). It has been indicated in the past that an atypical conformation of the "SC367CP" loop near the [2Fe]H portion of the six-iron active site (H-cluster) allows the Cys367 residue to adopt an "off-H+-pathway" orientation, promoting a facile transition of the cofactor to Hinact. Here, we investigated the electronic structure of the H-cluster in the oxidized state (Hox) that directly converts to Hinact under oxidizing conditions and the related CO-inhibited state (Hox-CO). We demonstrate that both states exhibit two distinct forms in electron paramagnetic resonance (EPR) spectroscopy. The ratio between the two forms is pH-dependent but also sensitive to the buffer choice. Our IR and EPR analyses illustrate that the spectral heterogeneity is due to a perturbation of the coordination environment of the H-cluster's [4Fe4S]H subcluster without affecting the [2Fe]H subcluster. Overall, we conclude that the observation of two spectral components per state is evidence of heterogeneity of the environment of the H-cluster likely associated with conformational mobility of the SCCP loop. Such flexibility may allow Cys367 to switch rapidly between off- and on-H+-pathway rotamers. Consequently, we believe such structural mobility may be the key to maintaining high enzymatic activity while allowing a facile transition to the O2-protected state.

Self-Stigma's Effect on Psychosocial Functioning Among People With Mental Illness.

ABSTRACT: Consequences of self-stigma exhibit a four-step regressive model from being aware of public stigma, to agreeing with it, to applying it to oneself, to resulting harm on the self. We hypothesize the relationship between self-stigma and psychosocial functioning is mediated by three constructs: the why try effect, stigma stress coping resources, and personal recovery. Two hundred eight people with depressive and bipolar disorders participated the study. Data partially supported the regressive model of self-stigma. Awareness was not found to be associated with other regressive stages. The model representing the path between self-stigma-harm and psychosocial functioning was significant and robust. The path was mediated by the why try effect and personal recovery. Findings echo the growing body of research attempting to describe outcomes of self-stigma, in this case, psychosocial functioning. Programs meant to erase self-stigma, and its effect on functioning should incorporate the why try effect and personal recovery as strategic ingredients.

Weight Self-Efficacy and Recovery Among African-Americans With Serious Mental Illness and High Body Weight.

ABSTRACT: Many African-Americans with serious mental illness fail to engage in evidence-based programs that positively affect weight management. We examined how having a weight-related physical illness correlated with self-efficacy, recovery, and quality of life by contrasting illnesses with symptoms that are obviously perceived ( e.g. , sleep apnea and pain related to weight) versus those that are not ( e.g. , hypertension). African-Americans with serious mental illness who were overweight (body mass index ≥25) completed the Weight Efficacy Lifestyle Questionnaire, Recovery Assessment Scale, and Quality of Life Scale in this study assessing the impact of a program on weight and health. Silent weight-related physical disorders were not found to correlate with quality of life, recovery, or weight self-efficacy. Differences in recovery were found in people with versus without sleep apnea and weight-related pain. Findings suggest future directions for affirming approaches to promote engagement among African-Americans with serious mental illness in weight management programs.

Does the peer-led Honest, Open, Proud program reduce stigma's impact for everyone? An individual participant data meta-regression analysis.

PURPOSE: Many people with mental illness experience self-stigma and stigma-related stress and struggle with decisions whether to disclose their condition to others. The peer-led Honest, Open, Proud (HOP) group program supports them in their disclosure decisions. In randomized controlled trials, HOP has shown positive effects on self-stigma and stigma stress on average. This study examined individual predictors of HOP outcomes and tested the hypothesis that stigma stress reduction at the end of HOP mediates positive HOP effects at follow-up. METHODS: Six RCTs were included with data at baseline, post (after the HOP program) and at 3- or 4-week follow-up. Baseline variables were entered in meta-regression models to predict change in self-stigma, stigma stress, depressive symptoms and quality of life among HOP participants. Mediation models examined change in stigma stress (post) as a mediator of HOP effects on self-stigma, depressive symptoms, and quality of life at follow-up. RESULTS: More shame at baseline, and for some outcomes reduced empowerment, predicted reduced HOP effects on stigma stress, self-stigma, depressive symptoms, and quality of life. Younger age was related to greater improvements in stigma stress after the HOP program. Stigma stress reductions at the end of HOP mediated positive effects on self-stigma, depressive symptoms and quality of life at follow-up. CONCLUSION: Participants who are initially less burdened by shame may benefit more from HOP. Stigma stress reduction could be a key mechanism of change that mediates effects on more distal outcomes. Implications for the further development of HOP are discussed.

Honest, Open, Proud (HOP) for people with mental illness in Hong Kong: a randomized controlled trial.

BACKGROUND: Self-stigma among people with mental illness is negatively associated with personal and clinical recovery. Due to the concealable nature of mental illness, people with mental illness experience constant struggles between concealment and disclosure. Disclosure of mental health challenges can potentially minimize negative impacts of self-stigma and enhance self-esteem and sense of empowerment. Honest, Open, Proud (HOP) is a peer-led intervention that promotes autonomous and dignified decisions about disclosure. PURPOSE: This study examined the effectiveness of HOP on concealment motivation, empowerment, self-stigma, stigma stress, and recovery among people with lived experience of mental illness in Hong Kong. METHODOLOGY: A total of 162 participants with a mean age of 45.38 were recruited and randomized into intervention group and waitlist control group. Participants in the intervention group were invited to attend a 6-session HOP group intervention. RESULTS: Significant improvement in optimism score from the empowerment scale was found in the intervention group compared to the waitlist control group and the effect was sustained at 1-month follow-up. However, significant changes were not found in other outcome variables. CONCLUSION: Only improvement in optimism was observed in the current study. Future study needs to examine the effects of HOP with further modification to maximize the benefit for people with lived experience of mental illness in the local context.

How do Americans perceive the stigma of leprosy?

The stigma of leprosy will have reduced effects if people cannot reliably perceive it. Two factors impact these perceptions: familiarity and entitativity. One hundred and forty-five participants tested this assertion using an online platform to complete measures of stigma about leprosy as well as measures of familiarity and entitativity. The group of 145 completed the same measures of stigma, entitativity, and familiarity 1 week later. Standard deviations of time 1 and time 2 measures of stigma were used as indices of consistent (reliable) perceptions at the individual level. Results showed partial support for familiarity being positively associated with reliable responding. Moreover, high entitativity scores were associated with greater stigma perceptions at time 1 and time 2. Ongoing research on these indicators may be important in crafting future anti-stigma programs for leprosy.

The stigma of alcohol-related liver disease and its impact on healthcare.

People with alcohol-related liver disease (ALD) experience stigma and discrimination. This review summarises the evidence on stigma in healthcare and its implications for people with ALD, drawing from the literature on the stigma associated with mental illness and, specifically, alcohol use disorder (AUD). Public stigma, self-stigma and structural stigma all contribute to failure to seek help or delays in seeking help, inferior healthcare, and negative health outcomes, which increase the overall burden of ALD. Stigma can be experienced, but also anticipated and avoided, with both scenarios negatively impacting on ALD healthcare. Blaming people with ALD for their condition is central to the stigma of ALD. Stigma affects ALD healthcare at all stages, from prevention, early detection and intervention, to allocation of scarce resources in liver transplantation. People with lived experience need to be empowered to lead action against the stigmatisation of patients with ALD. Promulgating a dynamic model of individual and social responsibility for AUD, a continuum model of harmful alcohol use, and establishing training on ALD-related stigma for healthcare professionals are strategies to address stigma. Integrating addiction and ALD services, providing stigma-free prevention, and overcoming the frequent separation of addiction services from general healthcare are necessary. Beyond healthcare, addressing social inequality, the social dimensions of ALD risk and outcomes, and ensuring equal access to services is necessary to improve outcomes for all people with ALD. More research is needed on the stigma of ALD in low- and middle-income countries and in countries with restrictive drinking norms. Interventions to reduce the stigma of ALD and facilitate early help-seeking need to be developed and evaluated.

Tendon loading in runners with Achilles tendinopathy: Relations to pain, structure, and function during return-to-sport.

We aimed to (1) compare pain, tendon structure, lower limb function, and Achilles tendon loads while running between limbs in runners with Achilles tendinopathy, and (2) explore the relations of pain, tendon structure, and lower limb function to Achilles tendon loads while running. Twenty runners with Achilles tendinopathy participated in this pilot study. Pain was assessed with questionnaires, quantitative sensory testing, and functional testing. Tendon morphology and mechanical properties were evaluated with ultrasound imaging, continuous shear wave elastography, and ultrasound imaging combined with dynamometry. Lower limb function was assessed with an established test battery. Achilles tendon loads were estimated from biomechanical data acquired during running. Compared to the least symptomatic limb, the most symptomatic limb had lower scores on the Victorian Institute of Sports Assessment - Achilles questionnaire and worse pain during drop countermovement jumping, hopping, and running. Tendon thickness and cross-sectional area were greater, and Young's modulus, drop countermovement jump height, and plyometric quotient during hopping were lower on the most symptomatic limb. Side-to-side differences in drop countermovement jump height were significantly associated with side-to-side differences in Achilles tendon peak forces and average loading rates during running. Various measures of pain, structure, and function differ between limbs in runners with Achilles tendinopathy during return-to-sport. Tendon forces, however, do not differ between limbs during comfortable running. In addition to measures that differ between limbs, measures of performance during drop countermovement jumping may aid in clinical decision-making during return-to-sport because they are associated with tendon forces while running.

Attitudes towards disclosing a mental illness: impact on quality of life and recovery.

PURPOSE: The decision whether to disclose a mental illness has individual and social consequences. Secrecy may protect from stigma and discrimination while disclosure can increase social support and facilitate help-seeking. Therefore, disclosure decisions are a key reaction to stigma. The first aim of this study was to test a newly developed scale to measure disclosure attitudes, the Attitudes to Disclosure Questionnaire (AtDQ). The second aim was to examine the impact of attitudes towards disclosing a mental illness on quality of life and recovery. METHODS: Among 100 participants with mental illness, disclosure attitudes, quality of life, recovery, benefits of disclosure, secrecy, social withdrawal, self-stigma, and depressive symptoms were assessed at weeks 0, 3 and 6. Psychometric properties of the AtDQ were analysed. Longitudinal associations between disclosure attitudes at baseline and quality of life and recovery after 6 weeks were examined in linear regressions. RESULTS: The analyses of the AtDQ indicated one-factor solutions, high acceptability, high internal consistency, and good retest reliability for the total scale and the subscales as well as high construct validity of the total scale. Results provided initial support for sensitivity to change. More positive disclosure attitudes in general and in particular regarding to family at baseline predicted better quality of life and recovery after 6 weeks. CONCLUSION: The current study provides initial support for the AtDQ as a useful measure of disclosure attitudes. Disclosing a mental illness, especially with respect to family, may improve quality of life and recovery of people with mental illness.

The Impact of Contact and Fame on Changing the Public Stigma of Mental Illness.

Many famous people have disclosed their mental illness to erase the harmful effects of stigma. This study examines the relative impact of disclosure stories from people who are or are not celebrities. We expected noncelebrities would be viewed as more similar and likeable and therefore have greater effects on stigma change. Research participants from an MTurk panel viewed self-disclosure stories from celebrity, Mariah Carey, or noncelebrity, Malia Fontecchio. Participants completed the Difference and Disdain Scale prior to reviewing the vignettes and immediately after each one. Participants also completed scales representing perceptions of fame, dissimilarity, and likeability of the person in each story. Results supported hypotheses: Mariah Carey was perceived as more famous, more dissimilar, and less likeable than Malia Fontecchio. Reading the Malia Fontecchio story led to greater improvement in disdain stigma than the Mariah Carey story. Implications for the varied role of celebrity status in stigma change are discussed.

Perceptions of difference and disdain on the self-stigma of mental illness.

BACKGROUND: People with mental illness are viewed as different and disdained by the general population leading to public stigma. When public stigma becomes internalized, it results in self-stigma. Content-less measures of stigma have shown to benefit studying public stigma, but research on self-stigma is limited. AIMS: This study sought to validate the use of content-less measures (Difference and Disdain) to assess self-stigma of mental illness. METHODS: Participants with lived experience (N = 291) completed a survey including measures of Difference and Disdain for self-stigma and outcomes assessing depression, self-esteem, recovery and the "Why Try" effect. Factor structure of Difference and Disdain across stages of self-stigma and their effects on harmful outcomes were analyzed. RESULTS: Factor structure was not supported. Reliability analysis suggested a two-stage conceptualization of self-stigma for Difference and Disdain characterized by early (i.e. aware, agree) and late stages (i.e. apply, harm). Disdain was found to independently contribute to significant harmful outcomes, especially in the late stages. CONCLUSIONS: Disdain seems to be the driver of the egregious effects of self-stigma for people with mental illness. Anti-stigma efforts should focus on stereotypes of Disdain in the future.

Debate: Stigma implications for diagnosing personality disorders in adolescents.

Diagnosing personality disorders (PDs) in adolescence is a complex and often controversial decision. While early diagnosis provides a pathway to treatment, stigmatizing labels might unintentionally increase prejudice and discrimination for youth and their families, resulting in harm and treatment avoidance. In this paper, we outline stigma-related considerations for diagnosing PDs in adolescence, including types of stigma (public stigma, self-stigma, associative stigma) and moderators of stigma (continuum beliefs, biogenetic attributions, PD sub-diagnosis). Research indicates that PDs are among the most stigmatizing diagnoses in adults, particularly among healthcare providers. Experiences with stigma may differentially impact adolescents, who are undergoing rapid changes in identity development and profound influences from educational systems, peers, and social media. Youth who receive mental health services (especially those embedded in schools) worry about whether and how to talk about a diagnosis. However, adolescents with significant behavioral symptoms are often seen as different from their peers even prior to a formal diagnosis. Systematic efforts are needed to anticipate and mitigate stigma-related impacts on adolescents who might be diagnosed with PDs.

Difference and Disdain as Indicators of the Public Stigma of Mental Illness.

ABSTRACT: Viewing a stigmatized group as different from everyone else is believed to be a contentless stigma that leads to disdain. This study tests whether three emotions-intergroup anxiety, anger, and empathy-mediate the path between difference and disdain. Six hundred thirty-eight research participants from MTurk provided valid responses to an online survey via Qualtrics. The survey used standardized measures of difference, disdain, intergroup anxiety, anger, and empathy. The hypothesized path model was tested using structural equation modeling (SEM). Fit indicators from SEM and corresponding betas supported a two-mediator model. Specifically, difference was found to be significantly associated with disdain. The path between the two was positively mediated by anger and negatively mediated by empathy. Difference and disdain may become important constructs in predicting and assessing stigma change. Perspective-taking that enhances empathy may prove especially useful for decreasing difference and disdain perceptions about people with mental illness.

Physicians' attitudes to disability pension - impact of diagnosis: an experimental study.

BACKGROUND: The purpose of this study is to increase understanding of physicians' attitudes towards disability pension applicants, and the impact of diagnosis. We hypothesize that physicians are more likely to think that patients with physical illnesses should get a disability pension than those with mental illness or alcohol dependence. Disability pension is an important source of income for those unable to work because of a disability and type of diagnosis should not impact accessing these benefits. METHODS: We conducted an experiment with a 2 by 3 factorial structure in Sweden. Each physician was randomly assigned one of six patient vignettes, with the same background description but with a different diagnosis. Each vignette had a diagnosis of either depression, alcohol dependence or low back pain, and was about a man or a woman. Logistic regression was used to examine the odds of a physician reporting that a patient should get a disability pension. Effects are reported in terms of odds ratios (ORs). RESULTS: 1414 Swedish registered physicians in psychiatry or general practice (24% response rate) completed the survey. Physicians assigned the alcohol dependent vignette had OR 0.45 (95% CI: 0.34 to 0.60) for perceiving that a patient should get a disability pension compared to physicians assigned the low back pain vignette. Physicians assigned the depression vignette had OR 1.89 (95% CI: 1.42 to 2.50) for perceiving that a patient should get a disability pension compared to physicians assigned the low back pain vignette. CONCLUSION: The patient diagnosis was associated with the physicians' response regarding if the patient should get a disability pension. A physician's perception is likely to impact a patient's access to disability pension.

Vicarious Stigma and Self-Stigma Experienced by Parents of Children with Mental Health and/or Neurodevelopmental Disorders.

The stigma of young children with mental health and/or neurodevelopmental disorders is experienced by their parents in at least two ways: self-stigma and vicarious stigma. Secrecy may diminish stigma through impression management or strategic disclosure. The present study explores the relationship between vicarious stigma, self-stigma, secrecy coping, depression, and quality of life. Additionally, we examine the structure of a novel measure of vicarious stigma. Fifty parents of children with mental health and/or neurodevelopmental disorders completed measures. Self-stigma and sadness due to vicarious stigma were significantly associated with greater depression and diminished quality of life. Higher secrecy coping was also associated with higher depression and lower quality of life, supporting the benefits of disclosure. This research meaningfully adds to our understanding of stigma in general, and as experienced by parents of children with mental health and/or neurodevelopmental disorders. Implications for ongoing stigma change development and evaluation are discussed.

Difference as an indicator of the self-stigma of mental illness.

BACKGROUND: People with mental illness are viewed as different from the general population resulting in public stigma. When public stigma becomes internalized, it leads to self-stigma. The most distal stage of self-stigma is harm which can lead to negative self-concepts that inhibit recovery. AIM: This study examines how perceptions of "differentness" reflect self-stigma. We developed the Differentness Self-Stigma Scale (DSSS) to assess four regressive stages of self-stigma - awareness, agreement, application, and harm - and aimed to see whether DSSS scores predict self-stigma more effectively than the Self-Stigma of Mental Illness Scale (SSMIS). METHOD: Participants with lived experience (N = 291) completed a survey including the DSSS, SSMIS and outcomes assessing depression, self-esteem, recovery and the "why try" effect. RESULTS: DSSS scores differed significantly from the SSMIS in the agreement and harm stages of self-stigma. Higher self-stigma scores on the DSSS harm subscale predicted lower self-esteem and higher depression scores. However, the DSSS did not demonstrate a regressive pattern between all four stages of self-stigma like the SSMIS. CONCLUSION: The increase of DSSS scores at the application stage may be explained by perceived public stigma (i.e. how the public understands differentness). Future research should unpack the effects of perceived difference on self-stigma for the DSSS.

Factors predicting help seeking for mental illness among college students.

BACKGROUND: Evidence supports the contribution of various stigma-related constructs to help-seeking. These constructs have yet to be tested in a single model among college students, a group highly affected by mental illness. AIMS: Using data from 153 college students, this study examines factors contributing to help seeking for mental illness. METHOD: Using path analysis, the current study evaluated a model of the relationship between level of familiarity, personal stigma, desired social distance, label avoidance, attitudes towards treatment seeking and intentions to seek treatment. RESULTS: Findings support a model of help-seeking describing the relationship between familiarity with mental illness, personal stigma, social distance, label avoidance, attitudes and intentions to seek treatment. CONCLUSIONS: Findings suggest label avoidance, attitudes towards treatment seeking and intentions to seek treatment might be augmented through interventions aimed at increasing college students' levels of familiarity, or intimate contact, with individuals with mental illness. Additional implications for practice and further research are addressed.

Investigation of the Unusual Ability of the [FeFe] Hydrogenase from Clostridium beijerinckii to Access an O2-Protected State.

[FeFe] hydrogenases are enzymes capable of producing and oxidizing H2 at staggering submillisecond time scales. A major limitation in applying these enzymes for industrial hydrogen production is their irreversible inactivation by oxygen. Recently, an [FeFe] hydrogenase from Clostridium beijerinckii (CbHydA1) was reported to regain its catalytic activity after exposure to oxygen. In this report, we have determined that artificially matured CbHydA1 is indeed oxygen tolerant in the absence of reducing agents and sulfides by means of reaching an O2-protected state (Hinact). We were also able to generate the Hinact state anaerobically via both chemical and electrochemical oxidation. We use a combination of spectroscopy, electrochemistry, and density functional theory (DFT) to uncover intrinsic properties of the active center of CbHydA1, leading to its unprecedented oxygen tolerance. We have observed that reversible, low-potential oxidation of the active center leads to the protection against O2-induced degradation. The transition between the active oxidized state (Hox) and the Hinact state appears to proceed without any detectable intermediates. We found that the Hinact state is stable for more than 40 h in air, highlighting the remarkable resilience of CbHydA1 to oxygen. Using a combination of DFT and FTIR, we also provide a hypothesis for the chemical identity of the Hinact state. These results demonstrate that CbHydA1 has remarkable stability in the presence of oxygen, which will drive future efforts to engineer more robust catalysts for biofuel production.

Challenges to welcoming people with mental illnesses into faith communities.

Faith communities are important to the psychiatric care of people with mental illness. I distinguish the effects of two principles of becoming welcoming communities: compassion, in which the community accommodates members with mental illnesses so they are fully included, and dignity, which rests on the essential worth of everyone.