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We identified biologically relevant moderators of response to tumor necrosis factor (TNF)-α inhibitor, infliximab, among 60 individuals with bipolar depression. Data were derived from a 12-week, randomized, placebo-controlled clinical trial secondarily evaluating the efficacy of infliximab on a measure of anhedonia (i.e., Snaith-Hamilton Pleasure Scale). Three inflammatory biotypes were derived from peripheral cytokine measurements using an iterative, machine learning-based approach. Infliximab-randomized participants classified as biotype 3 exhibited lower baseline concentrations of pro- and anti-inflammatory cytokines and soluble TNF receptor-1 and reported greater pro-hedonic improvements, relative to those classified as biotype 1 or 2. Pretreatment biotypes also moderated changes in neuroinflammatory substrates relevant to infliximab's hypothesized mechanism of action. Neuronal origin-enriched extracellular vesicle (NEV) protein concentrations were reduced to two factors using principal axis factoring: phosphorylated nuclear factorκB (p-NFκB), Fas-associated death domain (p-FADD), and IκB kinase (p-IKKα/β) and TNF receptor-1 (TNFR1) comprised factor "NEV1," whereas phosphorylated insulin receptor substrate-1 (p-IRS1), p38 mitogen-activated protein kinase (p-p38), and c-Jun N-terminal kinase (p-JNK) constituted "NEV2". Among infliximab-randomized subjects classified as biotype 3, NEV1 scores were decreased at weeks 2 and 6 and increased at week 12, relative to baseline, and NEV2 scores increased over time. Decreases in NEV1 scores and increases in NEV2 scores were associated with greater reductions in anhedonic symptoms in our classification and regression tree model (r2 = 0.22, RMSE = 0.08). Our findings provide preliminary evidence supporting the hypothesis that the pro-hedonic effects of infliximab require modulation of multiple TNF-α signaling pathways, including NF-κB, IRS1, and MAPK.

Feminist Fans and Their Connective Action on Twitter K-Pop Fandom

Objective To evaluate the development and implementation of clinical practice guidelines for the management of depression globally. Methods We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries. Findings We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence. Conclusion Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost-effectiveness and impact on health outcomes. [phrase omitted] [phrase omitted] Objectif Evaluer le developpement et la mise en reuvre des directives de pratique clinique pour la gestion de la depression dans le monde. Methodes Nous avons effectue une revue systematique des directives existantes en matiere de gestion de la depression chez les adultes souffrant de troubles depressifs majeurs ou de troubles bipolaires. Pour chaque directive identifiee, nous avons verifie le degre de conformite vis-a-vis des mesures de qualite du developpement des directives (transparence des processus d'elaboration des directives et de leur financement, composition multidisciplinaire du groupe d'auteurs, revue systematique des etudes d'efficacite comparative) ainsi que de la mise en reuvre (indicateurs de qualite). Nous avons confronte les directives des pays a faible et moyen revenu avec celles des pays a haut revenu. Resultats Nous avons identifie 82 directives de pratique clinique nationales et 13 directives de pratique clinique internationales dans 83 pays et en 27 langues. Les processus d'elaboration des directives et les sources de financement etaient explicitement indiquees dans une moindre proportion chez les pays a faible et moyen revenu (8/29; 28%) par rapport aux pays a haut revenu (35/58; 60%). Le nombre de directives redigees par un groupe d'auteurs multidisciplinaire etait moins eleve dans les pays a faible et moyen revenu (2/29; 7%) que dans les pays a haut revenu (22/58; 38%). Une revue systematique de l'efficacite comparative a ete menee pour 31% (9/29) des directives dans les pays a faible et moyen revenu, contre 71% (41/58) des directives dans les pays a haut revenu. Seulement 10% (3/29) des directives emises par les pays a faible et moyen revenu et 19% (11/58) de celles emises par les pays a haut revenu comprenaient un programme d'evaluation des indicateurs de qualite ou de l'adherence aux recommandations. Conclusion La mise en reuvre des directives est mal planifiee, mal analysee et mal mesuree. Reduire les disparites de developpement et de mise en reuvre des directives dans les pays a faible et moyen revenu est une priorite. A l'avenir, ces directives devraient prevoir des strategies d'execution des recommandations, mais aussi d'evaluation de la faisabilite, de la rentabilite et de l'impact sur l'etat de sante. [phrase omitted] Objetivo Evaluar la elaboracion e implementacion de las directrices de practica clinica para el tratamiento de la depresion a nivel mundial. Metodos Se realizo una revision sistematica de las directrices existentes para el tratamiento de la depresion en adultos con trastorno depresivo mayor o bipolar. Por cada directriz identificada, se evaluo el cumplimiento de las medidas de calidad de elaboracion de directrices (como la transparencia en los procesos de elaboracion de directrices y su financiamiento, la composicion del grupo multidisciplinario de autores, la revision sistematica del estudio de eficacia comparativo) y la implementacion (como los indicadores de calidad). En este contexto, se compararon las directrices de los paises de ingresos bajos y medios con las de los paises de ingresos altos. Resultados Se identificaron las directrices de practica clinica a nivel nacional (82) y a nivel internacional (13) de 83 paises en 27 idiomas. Los procesos de elaboracion de directrices y las fuentes de financiamiento se especificaron de manera explicita en un porcentaje menor de directrices de los paises de ingresos bajos y medios (8/29; 28 %) en relacion con las de los paises de ingresos altos (35/58; 60 %). Un grupo de desarrollo multidisciplinario elaboro menos directrices (2/29; 7 %) para los paises de ingresos bajos y medios, en relacion con las de los paises de ingresos altos (22/58; 38 %). Ademas, se realizo una revision sistematica sobre la efectividad comparativa en el 31 % (9/29) de las directrices de los paises de ingresos bajos y medios, frente al 71 % (41/58) de las directrices de los paises de ingresos altos. Solo el 10 % (3/29) de las directrices de los paises de ingresos bajos y medios y el 19 % (11/58) de las directrices de los paises de ingresos altos describieron planes para evaluar los indicadores de calidad o el cumplimiento de las recomendaciones. Conclusion La implementacion de las directrices no se planifica, notifica ni evalua de manera adecuada a nivel mundial. Es prioritario reducir las desigualdades en la elaboracion y la implementacion de las directrices en los paises de ingresos bajos y medios. Las directrices que se elaboren en el futuro deberan presentar estrategias para implementar las recomendaciones y evaluar la viabilidad, la rentabilidad y el impacto en los resultados sanitarios., Introduction The rising prevalence and burden of depression worldwide disproportionately affect low- and middle-income countries. (1-4) Major depressive and bipolar disorders independently increase the risk for other chronic diseases, including [...]

Objective: Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder. Methods: A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria. Results: Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient. Conclusions: There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances. [ABSTRACT FROM AUTHOR]

Counterpublic research highlights the significance of counter-discourse in challenging dominant public spheres. Yet, less focus has been given to how counterpublic actors could destabilize the relationships within a dominant public to foster counter-discourse. I examine the creation of a feminist counterpublic within Twitter K-pop fandom to understand how oppositional actors can transform the toxic technocultures of the dominant public to create a counterpublic. Formed by feminist K-pop fans, this counterpublic defied toxic relational norms of the mainstream K-pop fandom, cultivating a culture where fans could critique problematic K-pop star text without renouncing their fan identity. I bring the concepts of relational schemas and scripts to the study of counterpublics to demonstrate how creating an alternative schema can be a tool of resistance. To do so, I highlight how feminist fans reappropriated existing relationship scripts and formulated new ones to modify the relational schema of the mainstream Kpop fandom. I argue that these relational strategies helped feminist fans regroup by creating opportunities for productive coexistence, facilitating an alternative relational schema around a critical fan identity. [ABSTRACT FROM AUTHOR]