Stem cell fate has been linked to the mechanical properties of their underlying substrate, affecting mechanoreceptors and ultimately leading to downstream biological response. Studies have used polymers to mimic the stiffness of extracellular matrix as well as of individual tissues and shown mesenchymal stem cells (MSCs) could be directed along specific lineages. In this study, we examined the role of stiffness in MSC differentiation to two closely related cell phenotypes: osteoblast and chondrocyte. We prepared four methyl acrylate/methyl methacrylate (MA/MMA) polymer surfaces with elastic moduli ranging from 0.1 MPa to 310 MPa by altering monomer concentration. MSCs were cultured in media without exogenous growth factors and their biological responses were compared to committed chondrocytes and osteoblasts. Both chondrogenic and osteogenic markers were elevated when MSCs were grown on substrates with stiffness <10 MPa. Like chondrocytes, MSCs on lower stiffness substrates showed elevated expression of ACAN, SOX9, and COL2 and proteoglycan content; COMP was elevated in MSCs but reduced in chondrocytes. Substrate stiffness altered levels of RUNX2 mRNA, alkaline phosphatase specific activity, osteocalcin, and osteoprotegerin in osteoblasts, decreasing levels on the least stiff substrate. Expression of integrin subunits α1, α2, α5, αv, β1, and β3 changed in a stiffness- and cell type-dependent manner. Silencing of integrin subunit beta 1 (ITGB1) in MSCs abolished both osteoblastic and chondrogenic differentiation in response to substrate stiffness. Our results suggest that substrate stiffness is an important mediator of osteoblastic and chondrogenic differentiation, and integrin β1 plays a pivotal role in this process.
Rumination is a cognitive process involving repetitive thoughts about negative experiences and emotions and is associated with psychopathology. Rumination has been implicated in mood and anxiety disorders, and there is a growing body of research on rumination in relation to eating disorder (ED) psychopathology. The current meta-analytic review focused on the literature addressing rumination and ED psychopathology. A comprehensive search process identified 38 studies, which primarily used cross-sectional designs with non-clinical samples. Results demonstrated that rumination was concurrently (r = 0.33) and prospectively (r = 0.22-0.23) associated with ED psychopathology, and that groups with ED psychopathology evidenced higher levels of rumination compared to non-ED control groups (g = 0.95), though no significant differences in rumination were observed when comparing anorexia nervosa to bulimia nervosa groups (g = 0.09). In addition, a narrative review of five experimental studies suggested that rumination in response to ED-related stimuli was related to increased negative affect and negative body-related cognitions across clinical and non-clinical samples. The type of rumination and sample population emerged as moderators of effect sizes, such that larger effects were observed among samples using ED-specific measures of rumination and heterogeneous samples compared to only non-clinical samples. Taken together, this literature demonstrates that rumination is a salient process in ED psychopathology, though the literature is characterized by methodological limitations and the need for more fully elaborated theories on the role of rumination in EDs. Findings are discussed in the context of existing models of rumination and ED psychopathology, with suggestions for future research in this area.
While these reviews have generally suggested varying patterns of neurocognitive deficits across EDs, there remain critical limitations regarding the methodological quality of these studies (e.g., the lack of prospective designs, consideration of confounding influences, or examination of interrelationships between neurocognitive domains and relationships between neurocognition and other relevant behavioral constructs). Specifically, we outline 10 key areas that are imperative to address in future research in this area in order to move our field forward.
Findings suggest that symptoms related to shape and weight concerns and guilt are central ED symptoms, while physical symptoms, self-esteem, and feeling overwhelmed are links that may underlie comorbidities in EDs. Results provided some support for the validity of network approaches, in that admission networks conveyed prognostic information. However, the lack of correspondence between symptom reduction and change in network strength indicates that future research is needed to examine network dynamics in the context of intervention and relapse prevention.
consistent with affect regulation models of eating pathology and suggest that binge-eating episodes may be maintained through a process of negative reinforcement.
Self-discrepancy theory (SDT) is a model of the relations between the self and affect which has been applied to the study of different types of psychopathology including depression, anxiety, and eating disorders. Although the theory itself is compatible with a transdiagnostic perspective on psychopathology, to date no systematic review of the literature has examined that possibility. We conducted a meta-analysis that synthesized the literature on self-discrepancy and psychopathology across a heterogeneous range of 70 studies. Results showed a small-to-medium association between self-discrepancy and psychopathology that was highly robust and similar in magnitude across domains. Furthermore, self-discrepancy was related to higher levels of a range of negative emotions and lower levels of a range of positive emotions. Meta-regression models showed that the effects were greater for actual:ideal discrepancy compared with actual:ought discrepancy for both depression and anxiety, which was contrary to the tenets of SDT which suggests specific associations between actual:ideal discrepancy and depression and actual:ought discrepancy and anxiety. Measurement type (i.e., idiographic vs. nomothetic) was a significant predictor of the effects for depression and anxiety, such that nomothetic measures evidenced greater associations compared with idiographic measures. Our findings could suggest that self-discrepancy represents a contributory factor related to a number of psychiatric disorders. However, the tenet of SDT suggesting unique associations between actual:ideal and actual:ought discrepancy and anxiety and depression respectively was not supported. Implications are discussed for future research on self-discrepancy and psychopathology including the study of mechanistic frameworks.
Objective: Evidence suggests that eating disorders (EDs) may be under-detected in males. Commonly used measures of EDs such as the Eating Disorder Examination-Questionnaire (EDE-Q) were initially developed within female samples, raising concern regarding the extent to which these instruments may be appropriate for detecting EDs in males. The current study used receiver operating characteristic (ROC) curve analysis to (a) examine the accuracy of the EDE-Q global score in correctly classifying males with and without clinically significant ED pathology, and (b) establish the optimal EDE-Q global clinical cutoff for males. Method: Participants were a clinical sample of 245 male ED patients and a control sample of 205 male undergraduates. Results: EDE-Q global scores demonstrated moderate-high accuracy in predicting ED status (area under the curve = 0.85, 95% CI: 0.82–0.89). The optimal cutoff of 1.68 yielded a sensitivity of 0.77 and specificity of 0.77. Discussion: Overall, results provide preliminary support for the discriminant validity of EDE-Q scores among males. However, concerns remain regarding the measure’s ability to comprehensively assess domains of disordered eating most relevant to males. Therefore, careful attention to the possibility for measurement bias and continued evaluation of the scale in males is encouraged.
Objective Evidence indicates that males account for a significant minority of patients with eating disorders (EDs). However, prior research has been limited by inclusion of small and predominantly non-clinical samples of males. This study aimed to (1) provide male clinical norms for widely used ED measures (Eating Disorder Examination Questionnaire [EDE-Q] and Eating Disorder Inventory-3 [EDI-3]) and (2) examine sex differences in overall ED psychopathology. Method Participants were 386 male and 1,487 female patients with an ED diagnosis aged 16 years and older who completed the EDE-Q and EDI-3 upon admission to a residential or partial hospital ED treatment program. Results Normative data were calculated for the EDE-Q (global and subscales) and the EDI-3 (drive for thinness, body dissatisfaction, and bulimia). Analyses of variance (ANOVAs) used to examine sex, ED diagnosis, and their interaction in relation to overall ED psychopathology revealed a consistent pattern of greater severity among females for ED psychopathology. Discussion This study provides clinical norms on the EDE-Q and the EDI-3 for males with clinically diagnosed EDs. It is unclear whether the greater severity observed in females reflects qualitative differences in ED presentation or true quantitative differences in ED severity. Additional research examining the underlying nature of these differences and utilizing male-specific ED measures with clinical samples is warranted.
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