Philosophy of psychiatry: theoretical advances and clinical implications.

Work at the intersection of philosophy and psychiatry has an extensive and influential history, and has received increased attention recently, with the emergence of professional associations and a growing literature. In this paper, we review key advances in work on philosophy and psychiatry, and their related clinical implications. First, in understanding and categorizing mental disorder, both naturalist and normativist considerations are now viewed as important - psychiatric constructs necessitate a consideration of both facts and values. At a conceptual level, this integrative view encourages moving away from strict scientism to soft naturalism, while in clinical practice this facilitates both evidence-based and values-based mental health care. Second, in considering the nature of psychiatric science, there is now increasing emphasis on a pluralist approach, including ontological, explanatory and value pluralism. Conceptually, a pluralist approach acknowledges the multi-level causal interactions that give rise to psychopathology, while clinically it emphasizes the importance of a broad range of "difference-makers", as well as a consideration of "lived experience" in both research and practice. Third, in considering a range of questions about the brain-mind, and how both somatic and psychic factors contribute to the development and maintenance of mental disorders, conceptual and empirical work on embodied cognition provides an increasingly valuable approach. Viewing the brain-mind as embodied, embedded and enactive offers a conceptual approach to the mind-body problem that facilitates the clinical integration of advances in both cognitive-affective neuroscience and phenomenological psychopathology.

Assessing the treatment response of lateral elbow tendinopathy using time-dependent ultrasonography, Doppler imaging, and elastography.

OBJECTIVE: To investigate the structural alterations, neovascularity, and elasticity of tendons and the relationship between elasticity and the Patient Rated Tennis Elbow Evaluation score after undergoing US-guided fenestration or surgery in patients with chronic lateral elbow tendinopathy. METHODS: Participants from the per-protocol population of a randomized trial conducted between October 2016 and June 2020 were included. The surgery and fenestration groups included 24 (mean age, 50 ± 7 years [standard deviation], 10 men) and 29 (47 ± 8 years, 18 men) participants, respectively. Ultrasound exams were performed at baseline, 6 months, and 12 months. Statistical analyses included linear mixed effects and generalized equation estimation models. RESULTS: Fenestration had no significant impact on tendon thickness (p = 0.46). Conversely, surgery significantly increased tendon thickness at 6 months (p < 0.0001) and remained elevated at 12 months (p = 0.04). Tendon echostructure exhibited a group effect (p = 0.03), indicating a higher proportion of pathological scores in the surgery group post-intervention compared to the fenestration group. Both groups showed a similar reduction in neovascularity from 6 to 12 months postintervention (p = 0.006). Shear-wave velocity increased in the fenestration group at 6 months (p = 0.04), while the surgery group experienced a nonsignificant decrease at 6 months, with some improvement at 12 months (p = 0.08). Changes in shear-wave velocity did not correlate with clinical outcome. CONCLUSIONS: Fenestration and surgery reduced tendon neovascularity over time. Unlike surgery, fenestration did not impact tendon size while improving tendon echostructure and elasticity. CRITICAL RELEVANCE STATEMENT: Fenestration and surgery equally alleviated symptoms and decreased tendon neovascularity in lateral elbow tendinopathy; however, fenestration did not alter tendon thickness and improved echostructure and shear-wave velocity, suggesting shear-wave velocity's potential for quantitatively monitoring tendon elasticity during healing. KEY POINTS: Reliable markers for monitoring healing response and informing treatment protocols in elbow tendinopathy are lacking. Fenestration and surgery reduced tendon neovascularity, while fenestration improved tendon echostructure and shear-wave velocity. Shear-wave velocity may provide quantitative measures to monitor tendon elasticity in response to treatment.

Beyond Conceptual Analysis: Social Objectivity and Conceptual Engineering to Define Disease.

In this article, I side with those who argue that the debate about the definition of "disease" should be reoriented from the question "what is disease" to the question of what it should be. However, I ground my argument on the rejection of the naturalist approach to define disease and the adoption of a normativist approach, according to which the concept of disease is normative and value-laden. Based on this normativist approach, I defend two main theses: (1) that conceptual analysis is not the right method to define disease and that conceptual engineering should be the preferred method and (2) that the method of conceptual engineering should be implemented following the principles of Alexandrova's account of social objectivity in the context of the definition of disease.

Occlusal Outcomes in Non-Robin Sequence Patients with Isolated Cleft Palate.

OBJECTIVES: 1. To assess the skeletal class occlusion and lateral cephalometry in children with isolated cleft palates (non-Robin sequence) and 2. to identify associations between these findings and pre-palatoplasty cleft palate measurements. STUDY DESIGN: Retrospective cohort study. SETTING: North American Institutional Tertiary Paediatric Center. PATIENTS: Our cleft database was reviewed, and patients were included if they had an isolated cleft palate without a Robin Sequence diagnosis, had a Furlow palatoplasty and had available per operative cleft palate measurements and available lateral cephalogram between 6 and 8 years old. Thirty-two patients matched to inclusion criteria. INTERVENTION: Furlow's Palatoplasty. MAIN OUTCOME AND MEASURES: Cleft size at palatoplasty, cephalometric measurements and skeletal occlusal classes were analysed. ANOVA was used to test the association between cephalometric measurements and occlusal classes. Results are presented as means with a 95% confidence interval. The association between cleft measurements and cephalometric parameters was tested with Spearman Correlation (rs). RESULTS: The skeletal occlusal outcome at 7 years old for this series of patients was: Class I: 19%; Class II: 59% and Class III: 22%. No single cleft measurement at palatoplasty was predictive of the skeletal occlusal outcome. A larger hard palate cleft was associated with a shorter antero-posterior maxilla. CONCLUSIONS: The skeletal occlusal class outcomes were similar to those found in a previous study in the literature. The occlusal prognosis appears to be better than in patients with Robin Sequence or with an associated cleft lip. No preoperative measurement was found to be associated with the occlusal outcome.

QTL mapping reveals novel genes and mechanisms underlying variations in H2S production during alcoholic fermentation in Saccharomyces cerevisiae.

Saccharomyces cerevisiae requirement for reduced sulfur to synthesize methionine and cysteine during alcoholic fermentation, is mainly fulfilled through the sulfur assimilation pathway. Saccharomyces cerevisiae reduces sulfate into sulfur dioxide (SO2) and sulfide (H2S), whose overproduction is a major issue in winemaking, due to its negative impact on wine aroma. The amount of H2S produced is highly strain-specific and also depends on SO2 concentration, often added to grape must. Applying a bulk segregant analysis to a 96-strain-progeny derived from two strains with different abilities to produce H2S, and comparing allelic frequencies along the genome of pools of segregants producing contrasting H2S quantities, we identified two causative regions involved in H2S production in the presence of SO2. A functional genetic analysis allowed the identification of variants in four genes able to impact H2S formation, viz; ZWF1, ZRT2, SNR2, and YLR125W, and involved in functions and pathways not associated with sulfur metabolism until now. These data point out that, in wine fermentation conditions, redox status, and zinc homeostasis are linked to H2S formation while providing new insights into the regulation of H2S production, and a new vision of the interplay between the sulfur assimilation pathway and cell metabolism.

Toward a new model of human resource management practices: construction and validation of the High Wellbeing and Performance Work System Scale.

Introduction: The integrated mutual gains model suggests five provisional sets of human resource management (HRM) practices that should benefit both employees and organizations and, as such, be explicitly designed to have a positive impact on wellbeing, which, in turn, can affect performance. Methods: An extensive review of the literature on scales that used a high-performance work system to assess HRM practices, as well as an extraction of items related to the theoretical dimensions of the integrated mutual gains model, were performed. Based on these preliminary steps, an initial scale with the 66 items found most relevant in the literature was developed and assessed regarding its factorial structure, internal consistency, and reliability over a two-week period. Results: Exploratory factorial analysis following test -retest resulted in a 42-item scale for measuring 11 HRM practices. Confirmatory factor analyses resulted in a 36-item instrument for measuring 10 HRM practices and showed adequate validity and reliability. Discussion: Even though the five provisional sets of practices were not validated, the practices that emerged from them were assembled into alternative sets of practices. These sets of practices reflect HRM activities that are considered conducive to employees' wellbeing and, consequently, their job performance. Consequently, the "High Wellbeing and Performance Work System Scale" was created. Nonetheless, future research is necessary to evaluate the predictive capacity of this new scale.

Association of nurse staffing and unit occupancy with mortality and morbidity among very preterm infants: a multicentre study.

OBJECTIVE: In a healthcare system with finite resources, hospital organisational factors may contribute to patient outcomes. We aimed to assess the association of nurse staffing and neonatal intensive care unit (NICU) occupancy with outcomes of preterm infants born <33 weeks' gestation. DESIGN: Retrospective cohort study. SETTING: Four level III NICUs. PATIENTS: Infants born 23-32 weeks' gestation 2015-2018. MAIN OUTCOME MEASURES: Nursing provision ratios (nursing hours worked/recommended nursing hours based on patient acuity categories) and unit occupancy rates were averaged for the first shift, 24 hours and 7 days of admission of each infant. Primary outcome was mortality/morbidity (bronchopulmonary dysplasia, severe neurological injury, retinopathy of prematurity, necrotising enterocolitis and nosocomial infection). ORs for association of exposure with outcomes were estimated using generalised linear mixed models adjusted for confounders. RESULTS: Among 1870 included infants, 823 (44%) had mortality/morbidity. Median nursing provision ratio was 1.03 (IQR 0.89-1.22) and median unit occupancy was 89% (IQR 82-94). In the first 24 hours of admission, higher nursing provision ratio was associated with lower odds of mortality/morbidity (OR 0.93, 95% CI 0.89 to 0.98), and higher unit occupancy was associated with higher odds of mortality/morbidity (OR 1.19, 95% CI 1.04 to 1.36). In causal mediation analysis, nursing provision ratios mediated 47% of the association between occupancy and outcomes. CONCLUSIONS: NICU occupancy is associated with mortality/morbidity among very preterm infants and may reflect lack of adequate resources in periods of high activity. Interventions aimed at reducing occupancy and maintaining adequate resources need to be considered as strategies to improve patient outcomes.

Measuring the Impact of MyLupusGuide in Canada: Results of a Randomized Controlled Study.

OBJECTIVE: This study was undertaken to assess the effects of a web-based program, MyLupusGuide, developed to facilitate self-management in systemic lupus erythematosus (SLE). METHODS: In this randomized controlled online study, participants received either immediate access to the MyLupusGuide site or delayed access starting on month 3. The primary outcome was the patient activation measure (PAM) score. Secondary outcomes included measurements of health status, self-efficacy, coping, perceived patient-physician relationship, and medication adherence. Outcomes were measured at the baseline visit and at the 3-month and 6-month follow-up visits. We used linear mixed modeling to compare PAM scores between the 2 groups at months 3 and 6. RESULTS: There were 541 participants included in this study. The mean ± SE age was 50 ± 14 years; 93% were female and 74% were White. The mean ± SE disease duration was 17 ± 12 years, and 56% visited MyLupusGuide at least once. The baseline mean ± SE PAM score was 61.2 ± 13, with 36% scoring low for perceived self-management skills. After 3 months of exposure to MyLupusGuide, there were no differences in terms of PAM scores between groups. In exploratory analyses, we found significant improvement in PAM scores in those who had low PAM scores at baseline and in male individuals. We observed significant improvements in self-efficacy before and after access to MyLupusGuide and delayed improvements at month 6 compared to month 3 in terms of mental health and emotional coping. CONCLUSION: MyLupusGuide increases self-efficacy but not patient activation. A total of 56% of participants visited the MyLupusGuide site during the study period. Individuals with lupus need support to become activated toward self-management behaviors.

Influence of ergosterol and phytosterols on wine alcoholic fermentation with Saccharomyces cerevisiae strains.

Sterols are a fraction of the eukaryotic lipidome that is essential for the maintenance of cell membrane integrity and its good functionality. During alcoholic fermentation, they enhance yeast growth, metabolism and viability, as well as resistance to high sugar content and ethanol stress. Grape musts clarified in excess lead to the loss of solid particles rich in sterols, resulting in sluggish and stuck fermentations. Two sterol sources can help Saccharomyces cerevisiae yeasts to adapt to fermentation stress conditions: ergosterol (synthesized by yeast under aerobic conditions) and phytosterols (plant sterols imported by yeast cells from grape musts under anaerobiosis). Little is known about the physiological impact of phytosterols assimilation in comparison with ergosterol and the influence of sterol type on fermentation kinetics parameters. Moreover, studies to date have analyzed a limited number of yeast strains. Thus, the aim of this work was to compare the performances of a set of Saccharomyces cerevisiae wine strains that represent the diversity of industrial wine yeast, fermenting with phytosterols or ergosterol under two conditions: sterol limitation (sterol starvation) and high sugar content (the most common stress during fermentation). Results indicated that yeast cell viability was negatively impacted by both stressful conditions, resulting in sluggish and stuck fermentations. This study revealed the huge phenotype diversity of the S. cerevisiae strains tested, in particular in terms of cell viability. Indeed, strains with better viability maintenance completed fermentation earlier. Interestingly, we showed for the first time that sterol type differently affects a wide variety of phenotype, such as viability, biomass, fermentation kinetics parameters and biosynthesis of carbon central metabolism (CCM) metabolites. Ergosterol allowed preserving more viable cells at the end of fermentation and, as a consequence, a better completion of fermentation in both conditions tested, even if phytosterols also enabled the completion of alcoholic fermentation for almost all strains. These results highlighted the essential role of sterols during wine alcoholic fermentation to ensure yeast growth and avoid sluggish or stuck fermentations. Finally, this study emphasizes the importance of taking into account sterol types available during wine fermentation.

Measuring the impact of an educational intervention in rheumatoid arthritis: An open-label, randomized trial.

Objectives: This study aims to determine whether patients with active rheumatoid arthritis (RA), either starting on or changing biological or targeted synthetic disease-modifying antirheumatic drugs (DMARDs), demonstrate better self-management safety skills three months after receiving a multidisciplinary educational intervention compared to patients receiving usual care. Patients and methods: Between October 2015 and October 2018 , this open-label, randomized-controlled trial included a total of 107 RA patients (27 males, 80 females; mean age: 60.2±10.4 years; range, 54 to 71 years) who were on treatment or in whom treatment was changed with a biological or targeted synthetic DMARD. The patients were randomized into two groups: Group 1 (n=57) received additional intervention with educational DVD and one teleconference session and Group 2 (n=55) received usual care and were offered the intervention at three months. All patients underwent a final visit at six months. At each visit, the patients completed the BioSecure questionnaire measuring the self-care safety skills, a behavioral intention questionnaire, and the Beliefs about Medicines Questionnaire (BMQ). Results: No significant difference was observed in the Biosecure score at three months between the two groups (p=0.08). After pooling the first three-month data in Group 1 and the last three-month data in Group 2, the mean score of the BioSecure questionnaire increased to 7.10±0.92 in the group receiving educational intervention (p<0.0001). This increase was maintained at six months in Group 2 (p=0.88). The rate of appropriate behavioral intention increased over time (76% at baseline and 85% at six months for both groups). There was no significant change in the BMQ (p=0.44 to 0.84). Conclusion: The development of an educational DVD followed by a teleconference seem to improve self-care safety skills of the patients in practical situations.

Species-Dependent Metabolic Response to Lipid Mixtures in Wine Yeasts.

Lipids are essential energy storage compounds and are the core structural elements of all biological membranes. During wine alcoholic fermentation, the ability of yeasts to adjust the lipid composition of the plasma membrane partly determines their ability to cope with various fermentation-related stresses, including elevated levels of ethanol and the presence of weak acids. In addition, the lipid composition of grape juice also impacts the production of many wine-relevant aromatic compounds. Several studies have evaluated the impact of lipids and of their metabolism on fermentation performance and aroma production in the dominant wine yeast Saccharomyces cerevisiae, but limited information is available on other yeast species. Thus, the aim of this study was to evaluate the influence of specific fatty acid and sterol mixtures on various non-Saccharomyces yeast fermentation rates and the production of primary fermentation metabolites. The data show that the response to different lipid mixtures is species-dependent. For Metschnikowia pulcherrima, a slight increase in carbon dioxide production was observed in media enriched with unsaturated fatty acids whereas Kluyveromyces marxianus fermented significantly better in synthetic media containing a higher concentration of polyunsaturated fatty acids than monounsaturated fatty acids. Torulaspora delbrueckii fermentation rate increased in media supplemented with lipids present at an equimolar concentration. The data indicate that these different responses may be linked to variations in the lipid profile of these yeasts and divergent metabolic activities, in particular the regulation of acetyl-CoA metabolism. Finally, the results suggest that the yeast metabolic footprint and ultimately the wine organoleptic properties could be optimized via species-specific lipid adjustments.

Treatment of chronic lateral epicondylosis: a randomized trial comparing the efficacy of ultrasound-guided tendon dry needling and open-release surgery.

OBJECTIVE: Evaluate the efficacy of ultrasound-guided dry needling and open-release surgery in reducing pain and improving function in workers with lateral epicondylosis refractory to at least 6 months of nonsurgical management. METHODS: We randomly assigned participants in a 1:1 ratio to receive dry needling or surgery. The primary outcome was the Patient Rated Tennis Elbow Evaluation (PRTEE) score at 6 months. Secondary outcome measures examined the impact of these techniques on professional activity, grip strength, and Global Rating of Change and Satisfaction scales. Statistical analyses included mixed-effects models and Fisher's exact tests. RESULTS: From October 2016 through June 2019, we enrolled 64 participants. Two participants were excluded, and data from 62 participants (48 ± 8 years, 33 men) with a mean duration of symptoms of 23 ± 21 months were analyzed. Baseline characteristics were similar in both groups. In the intention-to-treat analysis, no treatment-by-time interaction was observed (F(4,201) = 0.72; p = .58). The least-squares mean difference from baseline in PRTEE scores at 6 months was 33.4 (CI 25.2 - 41.5) in the surgery group and 26.9 (CI 19.4 - 34.4) in the dry needling group (p = .25). The proportion of successful treatment was 83% (CI 63 - 95%) and 81% (CI 63 - 93%) in the surgery and dry needling groups, respectively (p = 1.00). Changes in secondary outcomes were in the same direction as those of the primary outcome. No adverse event occurred. CONCLUSIONS: Ultrasound-guided dry needling resulted in comparable improvement in outcome scores on scales of pain, physical function, and global assessment of change and satisfaction than open-release surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02710682 KEY POINTS: • In patients with chronic lateral epicondylosis, ultrasound-guided tendon dry needling provides comparable therapeutic efficacy to open-release surgery. • Ultrasound-guided tendon dry needling allows for an earlier return to work and may be less costly than open-release surgery. • Care management guidelines should recommend treatment by ultrasound-guided tendon dry needling before open-release surgery.

Red blood cell-derived phosphatidylserine positive extracellular vesicles are associated with past thrombotic events in patients with systemic erythematous lupus.

BACKGROUND: Extracellular vesicles (EVs) released by blood cells have proinflammation and procoagulant action. Patients with systemic lupus erythematosus (SLE) present high vascular inflammation and are prone to develop cardiovascular diseases. Therefore, we postulated that the EV populations found in blood, including platelet EVs (PEVs) and red blood cell EVs (REVs), are associated with SLE disease activity and SLE-associated cardiovascular accidents. METHOD: We assessed autotaxin (ATX) plasma levels by ELISA, the platelet activation markers PAC1 and CD62P, ATX bound to platelets and the amounts of plasma PEVs and REVs by flow cytometry in a cohort of 102 patients with SLE, including 29 incident cases of SLE and 30 controls. Correlation analyses explored the associations with the clinical parameters. RESULT: Platelet activation markers were increased in patients with SLE compared with healthy control, with the marker CD62P associated with the SLE disease activity index (SLEDAI). The incident cases show additional associations between platelet markers (CD62P/ATX and PAC1/CD62P) and the SLEDAI. Compared with controls, patients with SLE presented higher levels of PEVs, phosphatidylserine positive (PS+) PEVs, REVs and PS+ REVs, but there is no association with disease activity. When stratified according to the plasma level of PS+ REVs, the group of patients with SLE with a high level of PS+ REVs presented a higher number of past thrombosis events and higher ATX levels. CONCLUSION: Incident and prevalent forms of SLE cases present similar levels of platelet activation markers, with CD62P correlating with disease activity. Though EVs are not associated with disease activity, the incidence of past thrombotic events is higher in patients with a high level of PS+ REVs.

Identification of Mitofusin 1 and Complement Component 1q Subcomponent Binding Protein as Mitochondrial Targets in Systemic Lupus Erythematosus.

OBJECTIVE: Mitochondria are organelles that exhibit several bacterial features, such as a double-stranded genome with hypomethylated CpG islands, formylated proteins, and cardiolipin-containing membranes. In systemic lupus erythematosus (SLE), mitochondria and their inner components are released into the extracellular space, potentially eliciting a proinflammatory response from the immune system. While cardiolipin and mitochondrial DNA and RNA are confirmed targets of autoantibodies, other antigenic mitochondrial proteins in SLE remain to be identified. The present study was undertaken to characterize the protein repertoire recognized by antimitochondrial antibodies (AMAs) in patients with SLE. METHODS: Using shotgun proteomic profiling, we identified 1,345 proteins, 431 of which were associated with the mitochondrial proteome. Immunoreactivities to several of these candidate proteins were assessed in serum samples from a local cohort (n = 30 healthy donors and 87 patients with SLE) using enzyme-linked immunosorbent assay, and further analyzed for associations with demographic and disease characteristics. RESULTS: We determined that IgG antibodies to the complement component C1q binding protein were significantly elevated in the patients with SLE (P = 0.049) and were also associated with lupus anticoagulant positivity (P = 0.049). Elevated levels of IgG antibodies against mitochondrial protein mitofusin 1 (MFN-1) were promising predictors of SLE diagnosis in our cohort (adjusted odds ratio 2.99 [95% confidence interval 1.39-6.43], P = 0.0044). Moreover, increased levels of anti-MFN-1 were associated with the presence of antiphospholipids (P = 0.011) and anti-double-stranded DNA (P = 0.0005). CONCLUSION: In this study, we characterized the mitochondrial repertoire targeted by AMAs in the setting of SLE. Our results indicate that autoantibodies can recognize secreted and/or surface proteins of mitochondrial origin. Profiling of the AMA repertoire in large prospective cohorts may improve our knowledge of mitochondrial biomarkers and their usefulness for patient stratification.

Comparison of Three Nursing Workload Assessment Tools in the Neonatal Intensive Care Unit and Their Association with Outcomes of Very Preterm Infants.

OBJECTIVE: Nursing workload assessment tools are widely used to determine nurse staffing requirements in the neonatal intensive care unit (NICU). We aimed to compare three existing workload assessment tools and assess their association with mortality or morbidity among very preterm infants. STUDY DESIGN: Single-center retrospective cohort study of infants born <33 weeks and admitted to a 52-bed tertiary NICU in 2017 to 2018. Required nurse staffing was estimated for each shift using the Winnipeg Assessment of Neonatal Nursing Needs Tool (WANNNT) used as reference tool, the Quebec Provincial NICU Nursing Ratio (QPNNR), and the Canadian NICU Resource Utilization (CNRU). Poisson regression models with robust error variance estimators were used to assess the association between nursing provision ratios (actual number of nurses/required number of nurses) during the first 7 days of admission and neonatal outcomes. RESULTS: Median number of nurses required per shift using the WANNNT was 25.0 (interquartile range [IQR]: 23.1-26.7). Correlation between WANNNT and QPNNR was high (r = 0.92, p < 0.0001), but the QPNNR underestimated the number of nurses per shift by 4.8 (IQR: 4.1-5.4). Correlation between WANNNT and CNRU was moderate (r = 0.45, p < 0.0001). The NICU nursing provision ratios during the first 7 days of admission calculated using the WANNNT (adjusted risk ratio [aRR]: 0.96, 95% confidence interval [CI]: 0.93-0.99) and QPNNR (aRR: 0.97, 95% CI: 0.95-0.99) were associated with mortality or morbidity. CONCLUSION: Lower nursing provision ratio calculated using the WANNNT and CNRU during the first 7 days of admission is associated with an increased risk of mortality/morbidity in very preterm infants. KEY POINTS: · NICUs use different nursing workload assessment tools.. · We validated three different nursing workload assessment tools used in the NICU.. · Nursing provision ratio is associated the risk of mortality/morbidity in preterm infants..

Challenges of Perceived Self-Management in Lupus.

OBJECTIVE: Systemic lupus erythematosus is a chronic autoimmune disease with varied and unpredictable levels of disease activity. The ability to self-manage lupus is important in controlling disease activity. Our objective was to determine levels of patient activation toward self-management in lupus. METHODS: We used baseline results from the MyLupusGuide study, which had recruited 541 lupus patients from 10 lupus centers. We used the Patient Activation Measure (PAM), a validated self-reported tool designed to measure activation toward self-management ability, as our primary variable and examined its association with demographic, disease-related, patient-provider communication and psychosocial variables captured in our study protocol. Univariable and multivariable linear regressions were performed using linear mixed models, with a random effect for centers. RESULTS: The mean ± SD age of participants was 50 ± 14 years, 93% were female, 74% were White, and the mean ± SD disease duration was 17 ± 12 years. The mean ± SD PAM score was 61.2 ± 13.5, with 36% of participants scoring in the 2 lower levels, indicating low activation. Variables associated with low activation included being single, having lower physical health status, lower self-reported disease activity, lower self-efficacy, use of more emotional coping and fewer distraction and instrumental coping strategies, and a perceived lack of clarity in patient-doctor communication. CONCLUSION: Low patient activation was observed in more than one-third of lupus patients, indicating that a large proportion of patients perceived that they are lacking in lupus self-management skills. These results highlight a modifiable gap in perceived self-management ability among patients with lupus.

Medicalization, Contributory Injustice, and Mad Studies.

One recent body of work has concerned medicalization and how it can create epistemic injustice. It focuses on medicalization as a hermeneutical process that shapes the conceptual framework(s) we use to refer to some conditions/experiences. In parallel, some scholars with lived experience of madness have started to explore the epistemic harms suffered by the Mad community. Building on this, I argue that the process of medicalization in psychiatry affects the Mad community in a specific way that has been overlooked in the literature on medicalization and epistemic injustice. That is, medicalization can create what is called "contributory injustice." This form of injustice occurs when marginalized communities have been able to create alternative hermeneutical resources, but these resources are dismissed or discredited by the dominant group. I argue that the emerging field of Mad Studies is a victim of this type of injustice when Mad experiences are unilaterally medicalized.

The dual role of amyloid-ß-sheet sequences in the cell surface properties of FLO11-encoded flocculins in Saccharomyces cerevisiae.

Fungal adhesins (Als) or flocculins are family of cell surface proteins that mediate adhesion to diverse biotic and abiotic surfaces. A striking characteristic of Als proteins originally identified in the pathogenic Candida albicans is to form functional amyloids that mediate cis-interaction leading to the formation of adhesin nanodomains and trans-interaction between amyloid sequences of opposing cells. In this report, we show that flocculins encoded by FLO11 in Saccharomyces cerevisiae behave like adhesins in C. albicans. To do so, we show that the formation of nanodomains under an external physical force requires a threshold number of amyloid-forming sequences in the Flo11 protein. Then, using a genome editing approach, we constructed strains expressing variants of the Flo11 protein under the endogenous FLO11 promoter, leading to the demonstration that the loss of amyloid-forming sequences strongly reduces cell-cell interaction but has no effect on either plastic adherence or invasive growth in agar, both phenotypes being dependent on the N- and C-terminal ends of Flo11p. Finally, we show that the location of Flo11 is not altered either by the absence of amyloid-forming sequences or by the removal of the N- or C-terminus of the protein.

Expression of the myeloid inhibitory receptor CLEC12A correlates with disease activity and cytokines in early rheumatoid arthritis.

The myeloid inhibitory receptor CLEC12A negatively regulates inflammation. Reduced CLEC12A expression enhances inflammation in CLEC12A knock-out mice with collagen antibody-induced arthritis. Moreover, CLEC12A internalisation augments human neutrophil activation. We thus postulated that CLEC12A expression on circulating myeloid cells of rheumatoid arthritis patients is associated with disease manifestations. Cell-surface, CLEC12A receptor expression was determined on circulating neutrophils and monocytes of eRA patients and of healthy donors. Generalized estimating equations model, Student's t-test and Spearman's correlations were performed to compare CLEC12A expression between groups and test its association with disease activity and clinical parameters. Plasma cytokines were measured by multiplex immunoassay. Patients with reduced neutrophil or monocyte CLEC12A expression at baseline and at 3 months have an increased simple disease activity index. Low baseline CLEC12A expression also correlates with a higher SDAI at 6 months. In contrast, positive correlations were observed between baseline CLEC12A expression and several cytokines. Moreover, neutrophil and monocyte CLEC12A expression is significantly higher in early rheumatoid arthritis patients at baseline than healthy controls. Circulating neutrophil and monocyte CLEC12A expression correlates with disease activity at baseline and is predictive of SDAI at later stages of the disease indicative of a regulatory role for CLEC12A in RA.